thiourea and 2-(2-aminoethyl)pyridine

The effect of histamine on bovine isolated retinal small arteries (internal diameter, approximately 240 microns) was studied. Histamine induced a concentration-dependent relaxation in 43 of 53 vessels. The histamine-induced relaxation involves primarily activation of H1-receptors, with H2-receptors also affected as evidenced by the effect of selective histamine-receptor agonists and antagonists. The histamine-induced relaxation was dependent on the endothelium and seem to involve release of both endothelium-derived relaxing factor (EDRF) and a product which was inhibited by indomethacin, probably prostaglandin I2 (prostacyclin). The development of tachyphylaxis to the action of histamine seemed to rely on desensitization of the vascular smooth muscle cells to the relaxing effect of EDRF.

Topics: Acetylcholine; Animals; Cattle; Cimetidine; Dimaprit; Endothelium, Vascular; Histamine; Muscle Relaxation; Pyridines; Pyrilamine; Receptors, Histamine; Retinal Artery; Tachyphylaxis; Thiourea

Using the cannula inserting method, the vasodilatory effects of histamine were analysed employing selective histamine H1- and H2-receptor agonists and antagonists in isolated, perfused rat common carotid arterial preparations which were preconstricted by a continuous infusion of phenylephrine with propranolol. Histamine, 2-pyridylethylamine (2-PEA) (a selective H1-agonist) and dimaprit (a selective H2-agonist) produced a vasodilation in a dose-related manner. The order of potency was histamine greater than dimaprit greater than 2-PEA. Histamine-induced dilations were significantly inhibited by either diphenhydramine (a selective H1-antagonist) or cimetidine (a selective H2-antagonist). 2-PEA-induced dilations were significantly inhibited by diphenhydramine but not by cimetidine. Dimaprit-induced dilations were significantly blocked by cimetidine but not by diphenhydramine. ACh-, histamine-, 2-PEA- and dimaprit-induced dilations were significantly suppressed by removal of the endothelium. From these results, it is concluded that (1) isolated rat common carotid arteries have both H1- and H2-receptors, (2) there are few vasoconstrictory H1-receptors, (3) both H1- and H2-receptors mediate only vasodilation but not vasoconstriction, and (4) EDRF from the endothelium might participate in histamine-induced vasodilation via not only H1- but also H2-receptors.

Topics: Acetylcholine; Animals; Carotid Arteries; Cimetidine; Dimaprit; Diphenhydramine; Dose-Response Relationship, Drug; Female; Histamine; In Vitro Techniques; Male; Pyridines; Rats; Rats, Inbred Strains; Receptors, Histamine H1; Receptors, Histamine H2; Saponins; Thiourea; Vasodilation

Intracerebroventricular (i.c.v.) injections of histamine (HA) to Vetbutal-anaesthetized rats elicited a biphasic pressure response: a fall of blood pressure (BP) in the first minute, followed by a rise in BP. The heart rate (HR) response was also biphasic: bradycardia in the first minute, followed by tachycardia. The H1-receptor agonist 2-pyridylethylamine (PEA) increased the fall in BP in the first minute in comparison with the HA group, and then elicited a rise in BP that was, however, much lower than that produced by HA. Throughout the experiment PEA produced essentially only a bradycardia. The H2-receptor agonist dimaprit elicited a single-phase pressor response, i.e. a rise in BP and did not elicit tachycardia. Intraventricular pretreatment of rats with naloxone greatly reduced the initial response (phase 1) in the first minute in HA groups by 77-83% and PEA groups by 83-100%. Naloxone given in small doses also reduced the fall in HR by 71-100% in those groups. The experimental results permit a conclusion that the phase 1 response, i.e. the fall in BP, results from excitation of H1-receptors. Thus we may propose that H1-receptors are involved in the action of naloxone. Naloxone in a dose of 0.1 microgram inhibited the hypertensive responses of HA after 25-30 min. The reduction reached 71%. Naloxone reduced the small rise in BP induced by PEA (10 micrograms) but totally blocked the rise in BP induced by dimaprit (50 micrograms). This blockade indicates that the central opioid system may transmit the total stimulating response (rise in BP) of H2 receptors induced by dimaprit. Participation of central opioid receptors in HA-stimulated responses has already been demonstrated in corticosterone secretion.

Topics: Animals; Blood Pressure; Cimetidine; Dimaprit; Hemodynamics; Histamine; In Vitro Techniques; Injections, Intraventricular; Male; Naloxone; Pyridines; Pyrilamine; Rats; Rats, Inbred Strains; Thiourea

Ring strips of monkey pulmonary veins precontracted with a high concentration of prostaglandin F2 alpha (PGF2 alpha) relaxed in a concentration-dependent manner in response to histamine. Treatment with mepyramine and/or famotidine attenuated the relaxation. 2-Pyridylethylamine (2PEA) and dimaprit caused relaxations in the precontracted preparations, which were inhibited by pretreatment with mepyramine and famotidine, respectively. Removal of endothelium reversed the histamine- and 2PEA-induced relaxations to dose-related contractions. On the other hand, the removal had no effect on the dimaprit-induced relaxations, which were significantly reduced by pretreatment with famotidine. Histamine-induced relaxations in the precontracted strips with endothelium in the presence and absence of famotidine were suppressed or abolished by treatment with methylene blue or hemoglobin but were unaffected by aspirin. It may be concluded that histamine-induced relaxation in monkey pulmonary veins precontracted with PGF2 alpha is mediated by H2-receptors in smooth muscle and H1-receptors in endothelium. Also, stimulation of the endothelial H1-receptors liberates an endothelium-derived relaxing factor.

Topics: Animals; Dimaprit; Endothelium, Vascular; Famotidine; Hemoglobins; Histamine; In Vitro Techniques; Macaca; Methylene Blue; Pulmonary Veins; Pyridines; Pyrilamine; Receptors, Histamine H1; Receptors, Histamine H2; Thiourea; Vasoconstriction; Vasodilation

In rats under a mild stress of restraint the interaction between central opioid receptors and histaminergic stimulation of the pituitary-adrenocortical activity was investigated indirectly through corticosterone secretion. In order to avoid a possible direct action on adrenal glands, all the tested drugs were administered intracerebroventricularly (icv). Naloxone an opioid antagonist and cimetidine, a H2- and mepyramine a H1-receptor antagonists were given 15 min before histamine and histamine agonists. One hour after histaminergic drug injection the rats were restrained for 10 min and decapitated. Histamine, 2-pyridylethylamine (PEA), a histamine H1-receptor agonist, and 4-methylhistamine (MeHA) and dimaprit, H2-receptor agonists, significantly intensified the stress-induced increase in serum corticosterone levels. Naloxone, given alone icv or ip, did not substantially alter the stress-induced corticosterone response. Like mepyramine naloxone abolished the corticosterone response to PEA in stressed rats. Naloxone also decreased significantly, though not totally, the corticosterone response to MeHA, dimaprit and histamine, its efficiency being similar to that of cimetidine, a H2-receptor antagonist. These results suggest that in stressed rats central opioid receptors are considerably involved in the histamine H1-receptor - and, to a lesser degree, in the H2-receptor stimulation of the hypothalamo-pituitary-adrenocortical axis.

Topics: Animals; Cimetidine; Corticosterone; Dimaprit; Histamine; Male; Methylhistamines; Naloxone; Pituitary-Adrenal System; Pyridines; Pyrilamine; Rats; Rats, Inbred Strains; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Restraint, Physical; Stress, Physiological; Thiourea

In vascular smooth muscle cells, the activation of histaminergic receptors of the H1 subtype induces an increase in cytosolic free calcium. This has been shown to involve the metabolism of inositol-containing lipids. Since according to its pharmalogical characteristics, cicletanine could be considered as an H1 antagonist, it was of interest to check whether the drug behaved as such with regard to phosphoinositide metabolism. Phosphoinositide metabolism was studied by measuring the 32P labelling of phosphatidylinositol (PI) and of its phosphorylated derivatives in cultured smooth muscle cells isolated from guinea-pig aorta and incubated in the presence or absence of various histaminergic agonists and/or antagonists. The results clearly demonstrate that the increase in 32P-PI could be selectively induced by treatment of cells with histamine or 2-pyridylethylamine dihydrochloride (2-PEA) (an H1 agonist) but not with the H2 agonist dimaprit. In addition, histamine- or 2-PEA-induced 32P-PI increase was inhibited by pretreatment of cells with the H1 antagonist mepyramine, whereas the H2 antagonist cimetidine was without effect. These data demonstrate that the histamine-induced 32P-PI increase is mediated through H1 receptors. Under the same experimental conditions, cicletanine was as effective as mepyramine with an IC50 value of 10(-6) M. The development of tension in arterial smooth muscle is under the control of variations of calcium concentration in the intracellular space. Therefore, the blockade by cicletanine of histamine-enhanced phosphoinositide turnover may participate in the mechanism by which the drug exerts its antihypertensive action.

Topics: Angiotensin II; Animals; Antihypertensive Agents; Aorta, Thoracic; Cells, Cultured; Dimaprit; Diuretics; Guinea Pigs; Histamine; Male; Muscle, Smooth, Vascular; Phenylephrine; Phosphatidylinositols; Pyridines; Pyrilamine; Thiourea

The present study was undertaken to investigate the possible mechanism of histamine cytoprotection against 0.6 N HCl-induced gastric lesions in rats by 1) examining functional alterations such as acid secretion, gastric motor activity and mucosal vascular permeability in response to histamine and by 2) comparing the effects of histamine with those of 2-(2-pyridil)-ethylamine (PEA), an H1-agonist and of dimaprit, an H2-agonist. Histamine (3-20 mg/kg s.c.) dose-dependently increased acid secretion, inhibited motor activity and reduced the mucosal lesions in response to 0.6 N HCl. Similar effects were observed dose-dependently with dimaprit (10-40 mg/kg s.c.), but not with PEA (10 mg/kg s.c.). The protective action of both histamine and dimaprit was attenuated significantly by cimetidine (100 mg/kg s.c.) and indomethacin (5 mg/kg s.c.), but not by tripelennamine (10 mg/kg s.c.), which by itself inhibited significantly motor activity and the lesions. Stimulation of acid secretion caused by histamine as well as dimaprit was antagonized significantly by cimetidine, whereas antigastric motor effects of these agents were decreased significantly by both cimetidine and indomethacin. Histamine and PEA increased significantly the vascular permeability as measured by Evans blue, but the increased vascular permeability caused by 0.6 N HCl was reduced markedly by both histamine and dimaprit. These results suggest that the mucosal protective action of histamine may be mediated at least partly by endogenous prostaglandins through stimulation of H2-receptors, and may be associated with the effect on gastric motor activity but not with that on the mucosal vasculature.

Topics: Animals; Cimetidine; Dimaprit; Gastric Acid; Gastric Mucosa; Gastrointestinal Motility; Histamine; Hydrochloric Acid; Indomethacin; Male; Pyridines; Rats; Rats, Inbred Strains; Receptors, Histamine H1; Receptors, Histamine H2; Thiourea; Tripelennamine

The H1-histaminergic agonists 2-pyridylethylamine (2-PEA) and 2-methylhistamine relaxed potassium-constricted, perfused, rabbit middle cerebral arteries at low concentrations (3 x 10(-11) to 3 x 10(-8) M) and constricted them at high concentrations (3 x 10(-7) to 3 x 10(-4) M). The relaxation and the contraction were not antagonized by propranolol (up to 3 x 10(-6) M) given 30 min before, suggesting that beta-adrenergic mechanisms were not involved. When 2-PEA was tested on arteries constricted with uridine triphosphate (UTP), similar results were obtained. In the UTP-constricted arteries, the 2-PEA-induced responses were competitively antagonized by 3 x 10(-9) M mepyramine. Together with previous work (Ea Kim et al., 1986), these results are compatible with the hypothesis that H1-receptors were responsible for both the relaxation and the contraction observed. When either indomethacin (10(-8), 3 x 10(-7), or 10(-5) M), dexamethasone (10(-5) M), or tranylcypromine (10(-5) or 10(-4) M) were tested on the response to 2-PEA or 2-methylhistamine, these inhibitors suppressed the relaxation or reversed it to a contraction. Furthermore, they potentiated the contraction induced by these agonists. These results favour the hypothesis that the H1-mediated relaxation in rabbit cerebral arteries may in part involve the release of prostaglandins, especially prostacyclin. The participation of such a prostanoid in histaminergic relaxation seems exclusively an H1-mediated mechanism, since the relaxation induced by the H2-agonist dimaprit (in the presence of mepyramine) was not antagonized by either indomethacin (3 x 10(-7) M) or tranylcypromine (10(-4) M).

Topics: Animals; Cerebral Arteries; Dimaprit; In Vitro Techniques; Indomethacin; Male; Methylhistamines; Muscle Relaxation; Muscle, Smooth, Vascular; Pyridines; Rabbits; Receptors, Histamine H1; Receptors, Histamine H2; Thiourea; Tranylcypromine

The effects of histamine and of H1- and H2-receptor agonists on the response to specific antigen were studied in isolated hearts taken from actively sensitized guinea-pigs. Histamine and H2-receptor agonists (dimaprit, impromidine) dose-dependently decrease the positive chronotropic and inotropic effects, and the severity of arrhythmias evoked by the challenge of sensitized hearts with specific antigen. Nordimaprit and the selective H1-receptor agonist 2-pyridyl-ethyl-amine (2-PEA) did not modify the patterns of cardiac anaphylaxis. The positive inotropic and chronotropic responses of the isolated heart to exogenous histamine appear to be partly reduced in the presence of dimaprit. The H2-receptor agonists decrease the amount of histamine released during cardiac anaphylaxis which is increased by cimetidine, while nordimaprit and PEA were ineffective, indicating an inhibitory function afforded by H2-receptors in cardiac anaphylaxis.

Topics: Anaphylaxis; Animals; Cimetidine; Dimaprit; Female; Guinea Pigs; Heart; Heart Rate; Histamine; Histamine H1 Antagonists; Histamine H2 Antagonists; In Vitro Techniques; Male; Myocardial Contraction; Pyridines; Thiourea

The H1-receptor agonist 2-pyridylethylamine (PEA), and the H2-receptor agonists dimaprit and impromidine administered intracerebroventricularly (i.c.v.) to conscious rats considerably increased the concentration of free fatty acids (FFA) in the blood serum. The hyperlipemic effect of PEA was abolished by mepyramine, a H1-receptor antagonist. Responses to dimaprit and impromidine were not antagonized by cimetidine. These results suggest that central H1-receptor stimulation elicits the hyperlipemic responses in rats. The role of central H2-receptors in this reaction is not clear.

Topics: Animals; Brain; Cimetidine; Dimaprit; Fatty Acids, Nonesterified; Hyperlipidemias; Imidazoles; Impromidine; Injections, Intraventricular; Male; Pyridines; Pyrilamine; Rats; Rats, Inbred Strains; Thiourea

Topics: Acetylcholine; Alprostadil; Animals; Asthma; Dimaprit; Immunoglobulin E; Isoproterenol; Male; Mice; Mice, Inbred BALB C; Muscle, Smooth; Prostaglandins F; Pyridines; Thiourea; Trachea

The vascular responses of isolated and perfused canine epicardial coronary arteries to histamine, 2-pyridylethylamine (2-PEA, a selective histamine H1-receptor agonist) and dimaprit (a selective histamine H2-receptor agonist) were studied. Histamine produced only a vasodilatation at small doses (less than 0.3 microgram) and a biphasic response, i.e., vasoconstriction followed by vasodilatation at large doses. 2-PEA produced only a vasoconstriction at small doses and at large doses a slight vasodilatation following vasoconstriction. Dimaprit usually induced only a vasodilatation. The selective histamine H1-receptor antagonist chlorpheniramine shifted the dose-response curves of histamine and 2-PEA for inducing vasoconstriction to the right. Cimetidine (a selective histamine H2-receptor antagonist) caused dose-dependent shifts of the dose-response curves of histamine and dimaprit for vasodilatations to the right. Chlorpheniramine did not attenuate the vasodilatations by 2-PEA and histamine. The removal of endothelial cells by an intraluminal injection of saponin (1 mg) did not affect the vascular responses to histamine, 2-PEA and dimaprit. These results indicate that there are 2 types of histamine receptors in canine epicardial coronary arteries: (i) a H1-receptor mediating vasoconstriction and (ii) a H2-receptor, which is not endothelium-dependent, mediating vasodilatation.

Topics: Animals; Chlorpheniramine; Cimetidine; Coronary Vessels; Dimaprit; Dogs; Endothelium, Vascular; Female; Histamine; In Vitro Techniques; Male; Pyridines; Receptors, Histamine; Saponins; Thiourea; Vasoconstriction; Vasodilation

The effects of histamine and several H1 and H2 receptor agents on Na+/H+ and Cl-/HCO-3 exchange systems of isolated gastric mucosal surface cells were studied. The cells were acid-loaded by the NH4Cl prepulse technique and the spontaneous Na+- and HCO-3-induced dissipation of the intracellular proton gradient (pHi) was followed using the metachromatic dye acridine orange. Histamine (10(-2-5) M) stimulates HCO-3-induced dissipation of the pHi but has no effect on Na+-induced or spontaneous dissipation. The H1 agonist 2-(2-aminoethyl)pyridine and the H2 agonist dimaprit also have no effect on Na+-induced or spontaneous pHi dissipation. However, both of these agents mimic the effect of histamine on HCO-3-induced dissipation, but only at a higher concentration (10(-3) M). The combination of 2-(2-aminoethyl)pyridine and dimaprit produces a histamine-like effect at lower concentrations (10(-5) and 10(-4) M). The effects of histamine are blocked by either the H1 antagonists diphenhydramine and pyrilamine or the H2 antagonists cimetidine and SKF 93479. The results suggest that the effect of histamine on HCO-3-induced dissipation of a pHi in gastric mucosal surface cells is mediated through a coordinated mechanism involving both H1 and H2 receptor sites.

Topics: Animals; Bicarbonates; Chlorides; Cimetidine; Dimaprit; Diphenhydramine; Gastric Acid; Gastric Mucosa; Histamine; Protons; Pyridines; Pyrilamine; Rabbits; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Sodium; Thiourea

Low doses (0.01, 0.1 mg/kg, i.p.) of histamine (HA) caused selection of significantly lower temperatures, and higher doses (0.5, 1.0 mg/kg) increased temperatures by mudpuppies in linear thermal gradients. Injection of the HA precursor, L-histidine (500 mg/kg) produced an increase in the temperatures selected. Results from injections of HA H1-receptor agonist (2-pyridylethylamine) and antagonist (pyrilamine), and H2-receptor agonist (dimaprit) and antagonist (cimetidine) had significant effects on thermoregulation; H1-receptors may mediate behavioral hyperthermia and H2-receptors behavioral hypothermia. Responses to these histaminic compounds are significantly influenced by the time of day at which the responses are measured and by season and acclimation temperature. The equivalent behavioral responses in both endotherms and ectotherms to agents which produce physiological hyperthermia and hypothermia are probably behavioral hypothermia ("cold seeking") and behavioral hyperthermia ("heat seeking"), respectively.

Topics: Animals; Body Temperature Regulation; Cimetidine; Dimaprit; Histamine; Histidine; Necturus; Pyridines; Pyrilamine; Receptors, Histamine; Thiourea

1,4-Dithiothreitol (DTT; 1 mM, 30 min preincubation) produced a small, non-specific potentiation of spasmogenic activity in longitudinal muscle strips of guinea-pig small intestine. A direct comparison of contractile responses elicited by histamine and a range of H1- and non-H1-receptor agonists indicated that DTT produced a significantly greater potentiation of H1-receptor responses. This apparently selective increase in tissue sensitivity to histamine H1-receptor agonists did not appear to be a consequence of the inhibition of histamine N-methyl transferase or diamine oxidase activity. Potentiation of the responses to histamine by DTT was still observed in the presence of SKF 91488 (10 microM) and aminoguanidine (1 microM). The potentiation elicited by DTT was readily reversed by the sulphydryl oxidizing agent dithiobis-(2-nitrobenzoic acid) (DTNB). This suggests that the mechanism of action of DTT involves the reduction of disulphide bonds. Exposure of ileal smooth muscle to DTT following desensitization with histamine (100 X EC50 [- DTT]) resulted in a 6.9 +/- 0.7 fold shift of the concentration-response curve to lower agonist concentrations. Conversely, following potentiation of the response to histamine with DTT, exposure of the tissue to desensitizing concentrations of histamine resulted in a dextral shift of the dose-response curve (dose ratio = 39.5 +/- 1.2) to higher agonist concentrations. The results of this study suggest that DTT may be a useful tool with which to investigate histamine H1-receptor mechanisms in ileal smooth muscle.

Topics: Acetylcholine; Animals; Dimaprit; Dithionitrobenzoic Acid; Dithiothreitol; Dose-Response Relationship, Drug; Female; Guanidines; Guinea Pigs; Histamine; Ileum; In Vitro Techniques; Male; Muscle Contraction; Muscle, Smooth; Pyridines; Pyrilamine; Receptors, Histamine; Receptors, Histamine H1; Thiourea

Intraventricular administration of histamine (HA) in conscious freely moving rats produces a dose-dependent pressor response and bradycardia. These responses are diminished profoundly when a second injection of HA is given within a short time after the first injection. In this study, the specific HA H1 agonist, pyridylethylamine, and the specific H2 agonist, impromidine, were used to examine the nature of this tachyphylaxis. Blood pressure and heart rate were measured directly from indwelling carotid catheters, and drugs were administered in three consecutive intraventricular injections to conscious freely moving rats at 30-min intervals. HA, the H2 agonist, impromidine and the combined injection of pyridylethylamine and impromidine induced tachyphylaxis of the pressor response. The H1 agonist, pyridylethylamine and the HA-N-methyltransferase inhibitor, SKF-91488 (homodimaprit) did not show tachyphylaxis. Heart rate responses were more complex and only HA demonstrated tachyphylaxis of the bradycardia. It is concluded that the tachyphylaxis of the pressor response caused by repeated injections of HA results from the desensitization of central HA H2 receptors.

Topics: Animals; Blood Pressure; Brain; Cardiovascular System; Dimaprit; Heart Rate; Histamine; Imidazoles; Impromidine; Injections, Intraventricular; Male; Pyridines; Rats; Rats, Inbred Strains; Receptors, Histamine H1; Receptors, Histamine H2; Thiourea

The relaxation produced by several H2-receptor agonists and forskolin was investigated on strips of guinea-pig lung parenchyma. Dimparit, 1 microM to 10 mM, 4-methyl histamine, 0.5 microM to 100 microM and impromidine, 10 nM to 1 microM, had no effect on the tone of the unstimulated strips of lung parenchyma but caused a dose-dependent relaxation of strips that were contracted by 2-pyridylethylamine (2-PEA), 15 microM. Forskolin, 10 nM to 4 microM, produced a dose-dependent relaxation of both the stimulated and unstimulated lung strips. The muscarinic antagonist atropine, 1 microM, and the beta 2-adrenoceptor antagonist propranolol, 10 microM, had no effect on the dose-response curve for dimaprit-induced relaxation of the lung strip. The dose-response curve for dimaprit was shifted to the right in a dose-dependent manner by increasing concentrations of a variety of H2-antagonists. Schild plots produced a straight line for all the H2-antagonists with slopes not significantly different from unity. The equilibrium dissociation constants for the H2-antagonists on the lung strip preparation were similar to those previously reported for inhibition of the chronotropic activity of histamine on guinea-pig right atria and inhibition of [3H]-tiotidine binding to homogenates of guinea-pig lung parenchyma.

Topics: Animals; Atropine; Colforsin; Dimaprit; Female; Guinea Pigs; In Vitro Techniques; Lung; Male; Muscle Relaxation; Muscle, Smooth; Propranolol; Pyridines; Receptors, Histamine; Receptors, Histamine H2; Thiourea

Histamine inhibited luminol-dependent chemiluminescence (CL) of granulocytes in a dose-dependent manner, with an ID50 of about 3 X 10(-5) M. Dimaprit, a selective H2-agonist, produced a histamine-like effect. Furthermore, cimetidine, ranitidine, and TZU 0460, which are selective H2-antagonists, but not mepyramine, a selective H1-antagonist, blocked the inhibitory effect of histamine on CL. Thus it may be concluded that the inhibitory effect of histamine is mediated via histamine H2-receptors. H1- and H2-antagonists per se, except at extremely high concentrations, had no effect on CL of granulocytes.

Topics: Cimetidine; Dimaprit; Granulocytes; Histamine; Histamine Antagonists; Humans; In Vitro Techniques; Luminescent Measurements; Luminol; Pyridazines; Pyridines; Pyrilamine; Ranitidine; Thiourea

Histamine H1 and H2 receptors are known to exist in uterine smooth muscle; however, neither receptor has been clearly identified in the uterine vasculature. In the present study, 12 nonpregnant ewes were chronically instrumented with catheters in the carotid artery, jugular vein, uterine arteries, and electromagnetic flow probes on the uterine arteries for continuous measurement of uterine blood flow. Dose response curves were determined for bolus injections of Histamine (1-10 micrograms), the H1 receptor agonist 2PEA (10-100 micrograms), and the H2 receptor agonist Dimaprit (30-300 micrograms) before H1 receptor blockade with pyrilamine, following H1 receptor blockade, and following H2 receptor blockade with metiamide. Uterine vasodilator responses to histamine and 2PEA were essentially abolished by pyrilamine, while responses to dimaprit were not altered. Following addition of metiamide, responses to histamine were reduced further and responses to dimaprit were abolished. Baseline uterine blood flow was not altered by either H1 or H2 receptor blockade or their combination. Intraarterial bolus injections of the mast cell histamine-releasing compound 48/80 (100-1000 micrograms) had no effect on uterine blood flow. These experiments demonstrate that the uterine vasculature of the ovine contains almost exclusively H1 receptors, does not contain compound 48/80 sensitive mast cells and is not dependent upon endogenous histamine to maintain blood flow.

Topics: Animals; Dimaprit; Female; Histamine; p-Methoxy-N-methylphenethylamine; Pyridines; Receptors, Histamine H1; Receptors, Histamine H2; Regional Blood Flow; Sheep; Thiourea; Uterus

Although the factors involved in the induction of gastric pathology have long been studied, the exact roles of the two histamine receptors in this process are still obscure. The aim of this study was to evaluate the consequences of the activation of histamine H1- and/or H2-receptors in the pathogenesis of gastric damage and antagonism of these pathological developments by specific antagonists. The following agents were used: histamine as H1- and H2H2-agonist; 2-pyridylethylamine (PEA) and mepyramine as H1-agonist and antagonist; dimaprit and ranitidine as H2-agonist and antagonist. Intravenous administration of the agonists caused definite gastric damage in rats. Both the antagonists inhibited histamine-induced gastric lesions, but the PEA and dimaprit-induced erosions could be prevented only by giving the specific H1- or H2-antagonist. In conclusion, activation of either H1- or H2-receptors can play a crucial role in the pathogenesis of histamine-induced gastric damage in rats.

Topics: Aminopyridines; Animals; Atropine; Dimaprit; Drug Interactions; Female; Histamine; Pyridines; Pyrilamine; Ranitidine; Rats; Rats, Inbred Strains; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Stomach Ulcer; Thiourea

The effect of intravenous histamine on intragallbladder pressure (GBp) and subsequent modification of the histamine response by H1- and H2-antagonists was investigated in an awake baboon model. Responses to specific H1- and H2-agonists were also examined in order to further elucidate gallbladder histamine responses. Gallbladder volume (GBv) was arbitrarily set at 60-70% of observed resting GBv, and drugs were then infused intravenously with continuous monitoring of GBp. Histamine administration resulted in a logarithmic dose--response curve with a maximal increase in GBp equal to 31.7 mm Hg at a dose of 0.0625 mg of histamine. Infusion of the H1-antagonist diphenhydramine hydrochloride (Benadryl) resulted in a decreased GBp response to histamine when compared to preblocker response at all doses studied. On the other hand, histamine response following administration of the H2-antagonist metiamide was significantly greater than the preblocker histamine response. Infusion of the H1-agonist 2-pyridylethlamine resulted in a dose-dependent increase in GBp similar to the histamine curve, while infusion of the H2-agonist dimaprit resulted in consistent decreases in GBp. These results extend previous observations in subprimate preparations and demonstrate the presence of both stimulatory H1-receptors and inhibitory H2-receptors in an in situ primate model.

Topics: Animals; Dimaprit; Dose-Response Relationship, Drug; Female; Gallbladder; Histamine; Histamine H1 Antagonists; Histamine H2 Antagonists; Papio; Pressure; Pyridines; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Thiourea

We have previously shown that histamine in the dose range of 1.0 X 10(-16) to 1.0 X 10(-14) M caused a linear increase in oxyntic cell carbonic anhydrase (CA) activity. A maximal dose of the H2 antagonist, cimetidine, reduced the action of histamine by only 74 +/- 7.8% suggesting a possible H1 component of histamine action on oxyntic cells. Using quantitative cytochemistry of CA activity in guinea-pig oxyntic cells, we compared the dose-response relationships (1.0 X 10(-17)-1.0 X 10(-9) M) of specific H2 (dimaprit, 4-methylhistamine, impromidine) and H1 (2-pyridylethylamine) agonists with histamine (H1 and H2). In addition, we studied the effects of the specific H2 antagonist, cimetidine, and H1 antagonist, mepyramine, on histamine, dimaprit and 2-pyridylethylamine-stimulated CA activity. We found that guinea-pig oxyntic cells respond to both H1 and H2 agonists. H1 agonists were more potent but less efficacious than H2 agonists. H2 agonists were more efficacious, but less potent than H1 agonists. Cimetidine (10(-10)-10(-8) M) was a competitive antagonist of dimaprit-stimulated CA activity. However, at higher doses (10(-5) M), cimetidine antagonism of histamine-stimulated CA activity was of a mixed noncompetitive and competitive type. Cimetidine and mepyramine exhibited both H2 and H1 antagonism, but their affinities for their respective agonists were greater. The data suggests that the oxyntic cell has receptors for both H1 and H2 agonists. H1 agonism is important at low concentrations of agonists. The H1 and H2 receptor components appear to be functionally linked.

Topics: Animals; Carbonic Anhydrases; Cimetidine; Dimaprit; Dose-Response Relationship, Drug; Female; Guinea Pigs; Histamine; Histamine H1 Antagonists; Histamine H2 Antagonists; Imidazoles; Impromidine; In Vitro Techniques; Methylhistamines; Parietal Cells, Gastric; Pyridines; Pyrilamine; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Thiourea

Responses to histamine agonists administered intraventricularly under ether anesthesia were analyzed to evaluate receptor mediation in histamine stimulation of prolactin and LH release in ovariectomized, estradiol-progesterone-treated rats (OVX-E2P-treated rats). Prolactin release was markedly increased by the H2-histamine agonists, 4-methyl histamine and Dimaprit. These effects were antagonized by metiamide, an H2-blocking agent. The H1-histamine agonist, 2-(2-pyridyl)ethylamine (PEA) in high doses released prolactin and its effect was partially prevented by metiamide. Mepyramine, and H1-antagonist, did not exert any effect on the release of prolactin enhanced by the histamine agonists. LH release was significantly increased after 4-methyl histamine administration. Its effect was weak and was blocked by metiamide. Neither Dimaprit nor PEA exhibited action on plasma LH levels. The results obtained with histamine agonists suggest that histamine evokes prolactin release in OVX,E2P-treated rats through H2-receptors. At present, conclusions on H2-receptor mediation in LH release induced by histamine cannot be drawn from these results. The above-mentioned data, however, conclusively discard a significant participation of H1-receptors.

Topics: Animals; Castration; Dimaprit; Female; Histamine; Histamine H1 Antagonists; Luteinizing Hormone; Methylhistamines; Metiamide; Pituitary Gland, Anterior; Prolactin; Pyridines; Pyrilamine; Rats; Thiourea

Histamine (10(-3)-10(-8) M) inhibits PHA-induced proliferation of human peripheral blood lymphocytes (HPBL). Inhibition is detected at low concentrations of PHA but is rarely observed at high PHA concentrations. The histamine type II (H2) receptor agonists dimaprit, impromidine and 4-methylhistamine (4MH) inhibit HPBL proliferation and the H2 antagonist, cimetidine, reverses histamine-induced suppression of HPBL proliferation. Lymphocyte proliferation is also inhibited by the H1 receptor agonists, 2-pyridylethylamine and 2-thiazoylylethylamine, but only at high concentrations (10(-3) and 10(-4) M). The H1 agonist 2-methylhistamine, suppresses PHA-induced proliferation of HPBL in analogous fashion to histamine. This effect is reversed by cimetidine but not by diphenhydramine suggesting that an H2 receptor interaction is involved.

Topics: Cell Division; Cells, Cultured; Dimaprit; Dose-Response Relationship, Drug; Histamine; Humans; Imidazoles; Impromidine; Lymphocytes; Methylhistamines; Phytohemagglutinins; Pyridines; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Thiazoles; Thiourea

1 The effect of intrarenal histamine, dimaprit (H2-agonist) and 2-(2-pyridyl) ethylamine (H1-agonist) on renin release was examined in anaesthetized dogs. 2 In dogs with intact kidneys, histamine and dimaprit administration resulted in renal vasodilatation, a two fold increase in urinary sodium excretion, and no change in renal renin release. 2(2-Pyridyl) ethylamine administration resulted in renal vasodilatation, a 25% decrease in urinary sodium excretion and a significant increase in renin release. 3 In dogs with non-filtering kidneys, dimaprit administration resulted in renal vasodilatation and a significant increase in renin release, while 2(2-pyridyl) ethylamine administration resulted in renal vasodilatation but no change in renin release. 4 Our data suggest that histamine is a potential participant in the release of renin through stimulation of H2-receptors, but it is a weak agonist. 5 In addition, the direct effect of histamine analogues on renin release is modulated by their effects on electrolyte excretion probably by influencing the renal chemoreceptor release of renin mediated by the macula densa.

Topics: Animals; Dimaprit; Dogs; Female; Histamine; Kidney; Male; Pyridines; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Renal Circulation; Renin; Sodium Chloride; Thiourea

In rats subjected to a mild stress of immobilization histamine, H1-receptor agonist 2-pyridylethylamine (PEA), and H2-receptor agonists, 4-methylhistamine (4-MHA) and dimaprit, given intraventricularly 60 min prior to stress, intensified the stress-induced increase of hypophyseal-adrenocortical response, evaluated indirectly through corticosterone concentration in blood serum. The effects were dose dependent and on a molar basis histamine and PEA were the most potent and 4-MHA and dimaprit were less effective, in this respect. The effect of histamine was almost totally blocked by both H1-receptor antagonists, mepyramine or chloropyramine, and by H2-receptor antagonists, metiamide or cimetidine. The corticosterone response to PEA was abolished by mepyramine, and the responses to 4-MHA or dimaprit were antagonized by cimetidine and metiamide. The response to the H1 agonist was not substantially altered by pretreatment with cimetidine, and the responses to the H2 agonists were not changed by mepyramine. These results suggest that in stressed rats the corticosterone response to histamine is mediated by both H1 and H2 central histamine receptors.

Topics: Animals; Corticosterone; Dimaprit; Histamine; Histamine Antagonists; Male; Methylhistamines; Pituitary-Adrenal System; Pyridines; Rats; Rats, Inbred Strains; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Stress, Physiological; Thiourea

In conscious rats histamine, the H1-receptor agonist 2-pyridylethylamine (PEA), and the H2-receptor agonists dimaprit and impromidine given intracerebroventriculary (i.c.v.) increased the hypophyseal-adrenocortical response, evaluated indirectly through the corticosterone concentration in the blood serum. On a molar basis histamine was the most potent drug whereas its agonists were less potent in inducing an increased corticosterone response. Impromidine however, was far more active than dimaprit and PEA. The effect of histamine was significantly yet not totally antagonized by either mepyramine, a H1-receptor antagonist, or cimetidine, a H2-receptor blocker. The combination of mepyramine and cimetidine caused a considerably stronger inhibition than that induced by either antagonist given separately. Mepyramine impaired the corticosterone response to PEA, and the responses to impromidine and dimaprit were significantly diminished by cimetidine. The results suggest that i.c.v. histamine increases the pituitary-adrenocortical activity via both H1- and H2-receptors, and there seems to be no significant prevalence of either of these receptors in mediating this action of histamine.

Topics: Animals; Cimetidine; Corticosterone; Dimaprit; Dose-Response Relationship, Drug; Histamine; Imidazoles; Impromidine; Male; Pituitary-Adrenal System; Pyridines; Pyrilamine; Rats; Rats, Inbred Strains; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Thiourea

Topics: Animals; Dimaprit; Female; Gallbladder; Guinea Pigs; Histamine; Male; Muscle Contraction; Muscle, Smooth; Pyridines; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Thiourea

The effect of direct intragastric artery infusion of prostaglandins E2 and I2, arachidonic acid, dimaprit (histamine H2 agonist), and 2',2'-pyridylethylamine (histamine H1 agonist) on gastric mucosal blood flow was examined in dogs to elucidate the relationship between gastric secretory state and mucosal blood flow in dogs. These compounds were chosen because of their diverse effect on gastric acid secretion. Gastric fundus blood flow was measured both electromagnetically with a flow probe around the left gastric artery which supplies the fundus almost exclusively, and by the radioactive microsphere technique. Intraarterial infusion of all the compounds resulted in gastric mucosal vasodilation even though PGE2, PGI2, and arachidonic acid inhibit gastric acid secretion, dimaprit stimulated gastric acid secretion, and 2',2'-pyridylethylamine does not affect gastric acid secretion. There was total agreement in the blood flow measurements by the two different techniques. Our data suggest that gastric acid secretion and gastric vasodilation are independently regulated. In addition, the validity of the studies in which the aminopyrine clearance indicates that prostaglandins are mucosal vasoconstrictors needs to be questioned because of the reliance of those measurements on the secretory state of the stomach.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Dimaprit; Dinoprostone; Dogs; Epoprostenol; Gastric Mucosa; Prostaglandins; Prostaglandins E; Pyridines; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Regional Blood Flow; Thiourea; Vasodilation

The role of histamine-1 receptors in modulating gastric acid secretion was evaluated in anesthetized dogs with gastric fistulas. Histamine receptor agonists were infused directly into the gastric artery supplying the fundus to avoid any systemic hemodynamic effects. Two experimental approaches were taken to try to determine whether histamine-1 receptors participate in the control of acid secretion. Firstly, we measured the effect of the H1-receptor antagonist, hydroxyzine dihydrochloride, on histamine and dimaprit stimulated acid secretion. Secondly, we measured the effect of H1-receptor agonist on dimaprit stimulated gastric secretion. Although H1-receptor antagonist enhanced stimulated gastric acid secretion to histamine, the antagonist also enhanced stimulated gastric acid secretion to dimaprit (H2-agonist), suggesting that the enhanced gastric acid secretion after administration of H1-receptor antagonist is not because of the inhibition of histamine receptor at the gastric fundus. In addition, 2 doses of H1-receptor agonist infused into the gastric fundus had no effect on dimaprit stimulated gastric acid secretion. These data suggest that H1-receptors do not modulate gastric acid secretion at the level of the gastric fundus in the dog.

Topics: Animals; Dimaprit; Dogs; Gastric Acid; Hemodynamics; Hydroxyzine; Pyridines; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Thiourea

Histamine, injected subcutaneously (0.3-10 mg/kg), produced a dose-related inhibition of the primary and secondary inflammation, and the development of the secondary lesions of rat adjuvant arthritis. Histamine was effective when given for short periods around the time of adjuvant administration and could also delay and possibly reverse an established arthritic response. The histamine H1-agonist, 2-(2-pyridyl)-ethylamine, inhibited rat adjuvant arthritis, whereas the histamine H2-agonists, impromidine and dimaprit, failed to affect the response. Metiamide, a histamine H2-antagonist (5 mg/kg), reduced the inflammation in the uninjected hind-paw and the development of secondary lesions. Histamine may have two effects on rat adjuvant arthritis, inhibiting the response via stimulation of H1-receptors and augmenting the response via stimulation of H2-receptors. Since histamine is known to bind to and to alter the reactivity of cells which are involved in the regulation of immune responsiveness, it is suggested that interactions with these cells are responsible for the observed effects of histamine.

Topics: Animals; Arthritis; Arthritis, Experimental; Dimaprit; Dose-Response Relationship, Drug; Female; Histamine; Metiamide; Pyridines; Rats; Rats, Inbred Strains; Receptors, Histamine H1; Receptors, Histamine H2; Thiourea; Time Factors

Topics: Animals; Arousal; Cimetidine; Dimaprit; Diphenhydramine; Dose-Response Relationship, Drug; Grooming; Histamine; Male; Mice; Pyridines; Receptors, Histamine; Thiourea

The possibility that histamine may play a functional role in modulating mast-cell secretion, as has been suggested for basophil degranulation, has both physiologic and pharmacologic implications. Therefore the capacity of histamine to influence rat peritoneal mast-cell (RPMC) cyclic AMP levels and reversed anaphylatic degranulation as reflected in the release of 3H-serotonin (5-HT) was examined. To ascertain that RPMC were functionally responsive to exogenous hormonal stimulation, assessment of prostaglandin (PG) D2 effects on cyclic AMP and 5-HT release were determined in parallel. Although PGD2 (100 microM) increased cyclic AMP and inhibited 5-HT release in the presence of 50 microM aminophylline, histamine (up to 1000 microM) was ineffective was ineffective in both. However, 1000 microM histamine in the presence of 500 microM aminophylline was capable of transiently increasing RPMC cyclic AMP (for 15 to 30 sec) and under these conditions of suppressing 5-HT release. The receptor subtype involved in the suppressive actions of histamine appeared to be of the H-1 type as reflected in the capacity of specific H-1 agonists to reproduce the inhibition of 5-HT release, whereas neither H-2 agonists nor H-2 antagonists had any influence. Thus, under conditions in which phosphodiesterase enzymatic action is impaired, histamine in extremely high concentrations is able to modulate mast-cell secretion. However, it seems very unlikely that this action of histamine has any physiologic significance.

Topics: Aminophylline; Animals; Cyclic AMP; Dimaprit; Dose-Response Relationship, Drug; Guanidines; Imidazoles; Impromidine; Kinetics; Male; Mast Cells; Methylhistamines; Prostaglandins; Prostaglandins D; Pyridines; Rats; Rats, Inbred Strains; Receptors, Histamine H1; Receptors, Histamine H2; Serotonin; SRS-A; Thiourea

Histamine, 4-methylhistamine and dimaprit induced a dose-dependent increase in the cyclic AMP content of chopped canine parotid gland in the presence of 3-isobutyl-1-methylxanthine. Metiamide, but not mepyramine, inhibited the effect of these agonists dose-dependently. The cyclic AMP content was also increased by 2-(2-pyridyl)ethylamine. This effect was completely blocked by propranolol. These results indicate that the cyclic AMP response to histamine in canine parotid gland is mediated by H2-receptors. Mepyramine enhanced the effect of histamine. However, 2-(2-pyridyl)ethylamine had no significant inhibitory effect on the cyclic AMP response to 4-methylhistamine. A combination of aminoguanidine and quinacrine potentiated the effect of histamine, though no difference was observed in the histamine concentration of the media with or without these inhibitors when determined at the end of incubation. This suggests that there exist active histamine-metabolizing systems in canine parotid gland.

Topics: Animals; Cyclic AMP; Dimaprit; Dogs; Female; Histamine; Histamine Antagonists; In Vitro Techniques; Male; Methylhistamines; Parotid Gland; Pyridines; Receptors, Histamine; Receptors, Histamine H2; Thiourea

Utilizing histamine and selective agonists for H1- and H2-receptors, we examined the pH dependence of histamine-stimulated tension changes in guinea-pig gallbladder, which contains both contracting H1-receptors and relaxing H2-receptors. In muscle strips contracted with histamine and pH 7.3, increasing pH to 7.8 raised tension further (P less than .025), while decreasing pH caused a fall in tension (P less than .025). The H2-agonist Dimaprit relaxed tension at pH 7.3 and increasing the pH decreased the relaxation (p less than .0125). Contractions in response to H1-agonist 2-pyridylethylamine at pH 7.3 were unchanged when pH was elevated but decreased when pH was lowered (P less than .05). Tension changes in response to slow pH alterations suggested that H1-receptor activity is inhibited below pH 7.1 and H2-receptor activity is inhibited above pH 7.6. These reversible changes in activity probably reflect changes at H1- and H2-receptors rather than alterations in the ionic species of histamine.

Topics: Acetylcholine; Animals; Dimaprit; Female; Gallbladder; Guinea Pigs; Histamine; Hydrogen-Ion Concentration; In Vitro Techniques; Muscle Contraction; Muscle, Smooth; Potassium Chloride; Pyridines; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Thiourea

Promethazine and cimetidine blocked the hypotensive actions of 2-pyridylethylamine, and H1 agonist and dimaprit, an H2 agonist, respectively, but not that of bovine parathyroid hormone fragment [bPTH-(1-34)]. Rats were treated repeatedly with the histamine releaser, compound 48/80, until the release could no longer produce a decrease in blood pressure. The hypotensive action of bPTH-(1-34) could still be seen. Rats with histamine partially depleted with one injection of compound 48/80 were injected with cimetidine and pyrilamine, and H1 antagonist, which together blocked the hypotensive action of subsequent injections of compound 48/80, but not that of bPTH-(1-34). These data suggest that the vasodilatory action of bPTH-(1-34) does not involve the release or action of histamine.

Topics: Animals; Blood Pressure; Cimetidine; Dimaprit; Female; Histamine; Hypotension; Male; p-Methoxy-N-methylphenethylamine; Parathyroid Hormone; Peptide Fragments; Promethazine; Propranolol; Pyridines; Rats; Thiourea

The submandibular gland in situ was perfused with blood through the glandular artery at constant pressure in anesthetized dogs, and all drugs were administered intra-arterially. During infusion of metiamide, histamine and 2-(2-pyridyl)ethylamine (PEA) produced salivary and vasodilator responses consisting of an early and a late component. The dose-response curves for respective components of the salivary and vasodilator responses to PEA were parallel with the corresponding curves for histamine and in producing these responses PEA was about 40 times less potent than histamine on a molar basis. During infusion of mepyramine, histamine and dimaprit produced only the early vasodilator response. The dose-vasodilator response curves to histamine and dimaprit were parallel, and dimaprit was about 750 times less potent than histamine on a molar basis. The present results support the conclusion obtained in a previous study that neuronal histamine receptors mediating the whole salivary and the late vasodilator response are exclusively of the H1-type and vascular histamine receptors mediating the early vasodilator response consist of both H1-and H2-type although the former is predominant.

Topics: Animals; Dimaprit; Dogs; Female; Histamine; Male; Pyridines; Receptors, Histamine; Regional Blood Flow; Salivation; Submandibular Gland; Thiourea; Vasodilation

Topics: Animals; Blood-Brain Barrier; Carotid Artery, Internal; Cerebrovascular Circulation; Dimaprit; Glucose; Histamine; Injections, Intra-Arterial; Male; Pyridines; Rats; Rats, Inbred Strains; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Thiourea; Urea; Vasodilation

The role of histamine-1 receptors in modulating gastric acid secretion was evaluated in anesthetized dogs with gastric fistulas. Histamine receptor agonists were infused directly into the gastric artery supplying the fundus to avoid any systemic hemodynamic effects. Two experimental approaches were taken to try to determine whether histamine-1 receptors participate in the control of acid secretion. Firstly, we measured the effect of H1-receptor antagonist, hydroxyzine dihydrochloride, on histamine and dimaprit stimulated acid secretion. Secondly, we measured the effect of H1-receptor agonist on dimaprit stimulated gastric secretion. Although H1-receptor antagonist enhanced stimulated gastric acid secretion to histamine, the antagonist also enhanced stimulated gastric acid secretion to dimaprit (H2-agonist), suggesting that the enhanced gastric acid secretion after administration of H1-receptor antagonist is not because of the inhibition of histamine receptor at the gastric fundus. In addition, two doses of H1-receptor agonist infused into the gastric fundus had no effect on dimaprit stimulated gastric acid secretion. These data suggest that H1-receptors do not modulate gastric acid secretion at the level of the gastric fundus in the dog.

Topics: Animals; Dimaprit; Dogs; Gastric Acid; Hemodynamics; Hydroxyzine; Pyridines; Receptors, Histamine; Receptors, Histamine H1; Thiourea

Topics: Acetazolamide; Animals; Anti-Inflammatory Agents; Arachidonic Acids; Dimaprit; Dogs; Drug Interactions; Female; Histamine; Histamine H1 Antagonists; Histamine H2 Antagonists; Hydroxyzine; Male; Pharmaceutical Vehicles; Prostaglandins; Pyridines; Receptors, Histamine H1; Receptors, Histamine H2; Stomach; Thiourea; Time Factors; Vasodilation

1 The role of histamine H1- and H2-receptors in mediating the cutaneous inflammatory response produced by exogenous histamine and the release of endogenous histamine from mast cells has been investigated by a method which permits simultaneous, quantitative measurement of vasodilatation, vascular permeability and oedema formation. 2 Histamine and the selective H1-receptor agonist, 2-(2-aminoethyl) pyridine, both produced vasodilatation, increased vascular permeability and oedema formation whereas the selective H2-receptor agonist, dimaprit, produced only vasodilatation. 3 Mepyramine and cimetidine both reduced the vasodilatation response to histamine, the combination of antagonists being superior to either antagonist alone. Mepyramine (but not cimetidine) virtually abolished extravascular albumin accumulation and oedema formation. 4 Mepyramine and cimetidine both reduced the vasodilatation response produced by active cutaneous anaphylaxis and compound 48/80. However, mepyramine was less effective in reducing the vascular permeability response to mast cell degranulation than to histamine. 5 In conclusion, the vasodilator response to histamine is mediated by both H1- and H2-receptors; the permeability response to histamine is mediated solely by H1-receptors. A combination of H1- and H2-receptor antagonists appears to be more effective than either antagonist alone in reducing cutaneous inflammatory reactions involving histamine.

Topics: Animals; Cimetidine; Dimaprit; Guinea Pigs; Histamine; Histamine Antagonists; Histamine H1 Antagonists; Histamine H2 Antagonists; Inflammation; Male; Mast Cells; Mathematics; Pyridines; Pyrilamine; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Skin; Thiourea; Vasodilation

Histamine stimulated cyclic AMP-dependent protein kinase activity in dispersed mucosal cells from guinea-pig gastric fundus (Ka = 5 microM). The H2-agonists dimaprit and impromidine produced similar effects, while the H1-agonist 2-(2-pyridyl) ethylamine had only a weak one. The H2-antagonist cimetidine competitively inhibited 0.1 mM histamine stimulation (Ki = 2 microM). In contrast, the H1-antagonist diphenhydramine had no effect up to 1 mM.

Topics: Animals; Cimetidine; Cyclic AMP; Dimaprit; Diphenhydramine; Enzyme Activation; Gastric Mucosa; Guanidines; Guinea Pigs; Histamine; Imidazoles; Impromidine; In Vitro Techniques; Protein Kinases; Pyridines; Receptors, Histamine; Receptors, Histamine H2; Thiourea

The histamine chronotropic response of rabbit atria appears to be controlled by both H1 and H2 receptors and can be blocked in part by either metiamide (an H2 antagonist) or diphenhydramine (an H1 antagonist), while both 2- and 4-methylhistamine (H1 and H2 agonists, respectively) stimulated the chronotropic response. At low agonist concentrations, the simultaneous presence of both H1 and H2 blockers results in considerably less inhibition than could be expected from calculations of individual inhibition data, suggesting that some sites behave as if they have both H1 and H2 properties. Additional compounds were tested for specific action on H1 and H2 receptors: 2-(2-pyridyl) ethylamine, reported to be an H1 agonist, appears to stimulate rabbit atria by releasing norepinephrine and guinea pig atria by releasing both norepinephrine and histamine; while dimaprit, reported to be an H2 agonist, may stimulate histamine receptors directly but has a nonspecific depressant action on rabbit atria which interferes with its use as an agonist in this species.

Topics: Animals; Dimaprit; Female; Guinea Pigs; Heart Rate; Histamine; Male; Methylhistamines; Pyridines; Rabbits; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Thiourea; Time Factors

Topics: Animals; Cholecystokinin; Dimaprit; Female; Gallbladder; Haplorhini; Histamine; Muscle, Smooth; Papio; Pressure; Pyridines; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Thiourea

Histamine inhibits the in vitro release of granulocytic lysosomal beta-glucuronidase when incubated with complement activated zymosan particles and this is an H2-receptor response. The highly specific histamine H2-receptor agonist, dimaprit, also inhibits this secretory enzyme release but is less potent (-log molar ED50 6.71 with histamine vs. -log ED50 5.97 with dimaprit, p less than 0.05). No change in beta-glucuronidase release was found with the H1-agonst, 2-(2 pyridyl)-ethylamine. The antagonist activity of metiamide was similar with the two agonists (KB = 2.9 x 10(-8) M with histamine and KB = 3.6 x 10(-8) M with dimaprit). Diphenhydramine did not change the granulocyte response to either histamine or dimaprit.

Topics: Adult; Dimaprit; Glucuronidase; Granulocytes; Histamine; Humans; In Vitro Techniques; Lysosomes; Metiamide; Neutrophils; Pyridines; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Thiourea; Zymosan

Histamine (3 and 10 mumoles) raised the blood pressure in the conscious goat when given i.c.v. but lowered it when given intravenously. The results with 2-PEA support the view that central H1-stimulation raises the blood pressure. However, the results with dimaprit do not exclude the participation of central H2-receptors in the effect of histamine on the blood pressure. It appears that in the goat the stimulation of central H1- and H2-receptors mediates opposite actions on behavour. H1-agonist increased and H2-agonist decreased the general activity of the animal.

Topics: Animals; Behavior, Animal; Dimaprit; Female; Goats; Hemodynamics; Histamine; Injections, Intraventricular; Pyridines; Receptors, Histamine H1; Receptors, Histamine H2; Thiourea