thiourea and 2-(2-aminoethyl)thiazole

Activation of histaminergic and noradrenergic/adrenergic neurons in the brain stimulates the release of the neurohypophysial hormones arginine vasopressin (AVP) and oxytocin (OT) and are involved the mediation of the hormone responses to physiological stimuli such as dehydration and suckling. We therefore investigated whether the two neuronal systems interact in their regulation of AVP and OT secretion in conscious male rats. When administered intracerebroventricularly (i.c.v.), histamine (HA) as well as the H1 receptor agonist 2-thiazolylethylamine or the H2 receptor agonist 4-methylHA stimulated AVP and OT secretion. Prior i.c.v. infusion of antagonists specific to alpha or beta adrenergic receptors or their subtypes did not significantly affect the hormone response to HA or the histaminergic agonists. Infused i.c.v. norepinephrine (NE) or epinephrine (E) increased AVP and OT secretion. Prior i.c.v. infusion of the H1 receptor antagonist mepyramine or the H2 receptor antagonist cimetidine significantly inhibited the AVP and OT responses to NE and the AVP response to E, whereas only cimetidine inhibited the OT response to E significantly. Systemic pretreatment with imetit, which by activation of presynaptic H3 receptors inhibits neuronal synthesis and release of HA, decreased the AVP and OT responses to NE and E significantly. In the doses used, HA and E had no significant effect on mean arterial blood pressure. NE increased mean arterial blood pressure 10% at 1 and 2.5 min, whereafter the blood pressure returned to basal level within 10 min. The results indicate that noradrenergic and adrenergic neurons stimulate AVP and OT secretion via an involvement of histaminergic neurons, which may occur at magnocellular neurons in the supraoptic and paraventricular nuclei of the hypothalamus. The stimulatory effect of the amines on neurohypophysial hormone secretion seems to be independent of a central action on blood pressure. In contrast, a functionally intact noradrenergic and adrenergic neuronal system seems not to be a prerequisite for a HA-induced release of AVP and OT. The present findings further substantiate the role of histaminergic neurons in the central regulation of neurohypophysial hormone secretion.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Cerebral Ventricles; Cimetidine; Epinephrine; Histamine; Histamine Agonists; Hypothalamus; Imidazoles; Infusions, Parenteral; Male; Methylhistamines; Norepinephrine; Oxytocin; Pituitary Gland, Posterior; Pyrilamine; Rats; Rats, Wistar; Receptors, Histamine H2; Thiazoles; Thiourea

Histamine (HA), 1-1000 microM, significantly stimulated both basal and forskolin-activated cAMP generation in chicken and adult hen retina. The action of HA was reproduced by the selective H2-receptor agonists dimaprit and 4-methyl-histamine, but not by the selective H1-receptor agonist 2-thiazolylethylamine, and it was antagonized by the specific H2-receptor blockers cimetidine and tiotidine, but not by the H1-receptor blocker mepyramine. In parallel experiments, dopamine, an established retinal neuromodulator acting through the D1-type of receptor, also stimulated basal and forskolin-driven adenylate cyclase activity in homogenate of chicken retina. It is suggested that chicken retina contains HA H2-receptors which are positively coupled to the adenylate cyclase system.

Topics: Adenylyl Cyclases; Animals; Cerebral Cortex; Chickens; Cimetidine; Colforsin; Cyclic AMP; Dimaprit; Dopamine; Female; Histamine; Histamine H1 Antagonists; Histamine H2 Antagonists; Male; Methylhistamines; Pyrilamine; Receptors, Histamine H1; Receptors, Histamine H2; Retina; Thiazoles; Thiourea

1. The modulatory action of histaminergic drugs: histamine; 2-(2-aminoethyl)thiazole (H1-agonist); dimaprit (H2-agonist); diphenhydramine (H1-receptor antagonist); and cimetidine (H2-receptor antagonist) on rat vas deferens contractions induced by electrical field stimulation (0.1 Hz, 1 pulse, 1 msec duration, supramaximal voltage) was studied either at different calcium concentrations in the nutrient fluid or after verapamil. 2. Histamine and 2-(2-aminoethyl)thiazole inhibited the electrically-evoked contractions (EEC). This effect was unchanged after verapamil. 3. Diphenhydramine potentiated the EEC. Verapamil added before the H1-receptor antagonist inhibited this action. 4. The effects of agonists and antagonists of H-receptors decreased with the increasing of calcium concentration. 5. The results obtained suggested the existence of heterogeneity of prejunctional H-receptors. The function of histaminergic drugs on adrenergic neurotransmission in field stimulated rat vas deferens is Ca(2+)-dependent.

Topics: Animals; Calcium; Cimetidine; Dimaprit; Diphenhydramine; Electric Stimulation; Histamine; In Vitro Techniques; Male; Muscle Contraction; Rats; Receptors, Histamine H1; Receptors, Histamine H2; Thiazoles; Thiourea; Vas Deferens; Verapamil

An investigation was made of the effects of H1 and H2 receptor agonists and antagonists on rabbit pancreatic exocrine secretion stimulated by secretin and cholecystokinin (CCK). The H1 agonist 2-thiazolylethylamine elicited dose-dependent increases in the rate of secretion. Increases in pancreatic juice flow and enzyme output were also noted after H2 antagonist cimetidine. In contrast, the H1 antagonist chlorpheniramine and H2 agonist dimaprit caused reductions in flow and enzyme output. The results suggest that H1 receptors have stimulative effects and H2 receptors have inhibitory effects on exocrine rabbit pancreas.

Topics: Animals; Chlorpheniramine; Cholecystokinin; Cimetidine; Dimaprit; Dose-Response Relationship, Drug; Female; Histamine H1 Antagonists; Histamine H2 Antagonists; Male; Pancreas; Rabbits; Receptors, Histamine H1; Receptors, Histamine H2; Secretin; Thiazoles; Thiourea

The effect of perivagal capsaicin treatment on gastric acid secretion induced by the histamine H2 receptor agonist, dimaprit dihydrochloride, and the effect of the histamine H1 receptor agonist, 2-thiazolylethylamine dihydrochloride, on gastric acid secretion were studied in acute gastric fistula rats anesthetized with urethane. The integrated secretory response for the 2 h following subcutaneous (s.c.) administration of dimaprit dihydrochloride (5-20 mg/kg) did not differ in capsaicin- compared to vehicle-treated rats. Administration of 2-thiazolylethylamine dihydrochloride (20 mg/kg s.c.) did not modify gastric acid secretion in untreated rats. The present study demonstrates that the previously reported reduction in the secretory response to histamine by perivagal capsaicin treatment is unrelated to histamine H1 or H2 receptor.

Topics: Anesthesia; Animals; Capsaicin; Dimaprit; Dose-Response Relationship, Drug; Gastric Acid; Injections, Subcutaneous; Male; Neurons, Afferent; Rats; Rats, Inbred Strains; Receptors, Histamine H1; Receptors, Histamine H2; Thiazoles; Thiourea; Vagus Nerve

Histamine H2-receptor antagonists cimetidine and oxmetidine, H2-receptor agonist dimaprit, H1-receptor antagonist chlorpheniramine and H1-receptor agonist 2-thiazolylethylamine were tested for their effects on unstimulated pancreatic exocrine secretion in anaesthetized rabbits fitted with an acute pancreatic cannula. Intravenous administration of H1 agonist induces a dose-dependent increase in pancreatic secretion but H1 antagonist have the opposite effects. Intravenous administration of H2 antagonists induces effects similar the ones produced after H1 agonist infusion. The implications of H1 and H2 receptors on exocrine pancreatic secretion are discussed.

Topics: Animals; Chlorpheniramine; Cimetidine; Dimaprit; Dose-Response Relationship, Drug; Female; Histamine H1 Antagonists; Histamine H2 Antagonists; Imidazoles; Kinetics; Male; Pancreas; Rabbits; Receptors, Histamine H1; Receptors, Histamine H2; Thiazoles; Thiourea

It has been shown that histamine (HA) stimulates prolactin (PRL) secretion via H2 receptors following intra-cerebroventricular infusion and via H1 receptors following systemic (intra-arterial) infusion. Since the effect of HA appears to be exerted at a suprapituitary level, we investigated the involvement of the tuberoinfundibular dopaminergic (TIDA) system in HA-induced PRL secretion in urethane-anesthetized male rats. HA infused intracerebroventricularly (30 micrograms) or intra-arterially (420 micrograms) decreased the dopamine (DA) concentration in pituitary portal blood by 30 and 23%, respectively. Blockade of DA receptors by pimozide did not prevent the stimulation of PRL secretion induced by intracerebroventricular infusion of HA or the H2 receptor agonist dimaprit. Furthermore, during DA receptor blockade intracerebroventricular infusion of the H1 receptor agonist 2-thiazolylethylamine inhibited PRL secretion. In contrast, pimozide prevented the stimulation of PRL secretion induced by intra-arterial infusion of HA and the H1 receptor agonist 2-thiazolylethylamine. In fact, under these conditions intra-arterial infusion of HA or the H2-receptor agonist dimaprit inhibited PRL secretion. During treatment with alpha-methyl-p-tyrosine, which reduced the hypothalamic DA content by 50%, HA infused intracerebroventricularly stimulated PRL secretion, while HA infused intra-arterially inhibited the secretion, which is in accordance with the results obtained during pimozide treatment. Cholinergic blockade by atropine did not prevent the HA-induced PRL release, excluding the possibility that the observed effect of pimozide is due to its anticholinergic property. We suggest that intracerebroventricular infusion of HA by activation of H2 receptors may stimulate PRL secretion partly via inhibition of the TIDA system and partly via other mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cerebral Ventricles; Dimaprit; Dopamine; Histamine; Infusions, Intra-Arterial; Injections, Intraventricular; Male; Neurons; Prolactin; Rats; Rats, Inbred Strains; Receptors, Histamine H1; Receptors, Histamine H2; Reference Values; Thiazoles; Thiourea

Controversy exists regarding the involvement of H1- or H2-receptors in the PRL-releasing activity of histamine (HA). This could be due to differences in the route of administration of HA and histaminergic compounds. Therefore, we studied the effect on PRL secretion of HA and HA-agonists infused intracerebroventricularly (ICV) or systemically (IA) either alone or in combination with HA-antagonists in male rats. HA administered ICV as well as IA stimulated PRL secretion dose dependently. The stimulatory effect of ICV-infused HA was blocked by the H2-receptor antagonist cimetidine (CIM) and mimicked by the H2-receptor agonists 4-methylhistamine (4-MeHA) and dimaprit (DIM). In contrast, the H1-receptor antagonist mepyramine (MEP) enhanced the PRL-releasing effect of HA while the H1-receptor agonist 2-thiazolylethylamine (2-TEA) had no significant effect. The stimulatory effect of IA-infused HA was blocked by the H1-receptor antagonist MEP and mimicked by the H1-receptor agonist 2-TEA, whereas the H2-receptor antagonist CIM enhanced the PRL-stimulatory effect of HA and the H2-receptor agonist DIM was without effect. 4-MeHA stimulated PRL secretion, but this effect was unrelated to stimulation of H2-receptors. The effect of ICV administered HA was unaffected by IA infused antagonists and the effect of IA administered HA was not altered by ICV infused antagonists. HA had no effect on the PRL release from isolated adenohypophyses, and HA did not stimulate PRL secretion in pituitary stalk-sectioned rats following IA infusion. The findings indicate that HA administered ICV exerts its PRL releasing activity via H2-receptors while HA administered IA stimulates PRL secretion via H1-receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cimetidine; Dimaprit; Histamine; Histamine H1 Antagonists; Male; Methylhistamines; Pituitary Gland, Anterior; Prolactin; Pyrilamine; Pyrimidinones; Rats; Receptors, Histamine; Thiazoles; Thiourea

When histamine (Hi) and other agonists were applied intraventricularly, Hi caused a dose-dependent inhibition of the avoidance response in rats; its ED50 was 3.60 micrograms. 1-methylHi, 1-methylimidazole acetic acid and imidazole acetic acid which are major metabolites of Hi produced no inhibitory effect even at 50 micrograms. H1-agonists (2-methylHi and 2-thiazolylethylamine) also depressed the avoidance response; their dose-response lines run parallel to that of Hi. The depressant effects of H2-agonists (4-methylHi and dimaprit) were relatively weak; their dose-response lines were not parallel to that of Hi. When antagonists were pretreated intravenously, Hi action was clearly antagonized by diphehydramine and pyrilamine, but not by cimetidine or ranitidine. Intraventricular injection of Hi mixed with cimetidine or ranitidine did not change the effect induced by Hi alone. The avoidance response was not affected by noradrenaline, dopamine or 5-hydroxytryptamine. Although acetylcholine (ACh) suppressed the avoidance response dose-dependently, its effect was much weaker than that of Hi. Pretreatment with cholinergic blocking drugs (atropine and scopolamine) antagonized ACh action but not Hi action. From these results, it is assumed that the inhibitory effect of Hi on the avoidance response is preferentially linked to the H1-receptor. After intraventricular application of 3H-Hi, the highest radioactivity was determined in the hypothalamus.

Topics: Acetylcholine; Animals; Avoidance Learning; Dimaprit; Diphenhydramine; Dose-Response Relationship, Drug; Histamine; Histamine Antagonists; Hypothalamus; Injections, Intraventricular; Kinetics; Male; Methylhistamines; Pyrilamine; Rats; Rats, Inbred Strains; Scopolamine; Thiazoles; Thiourea

The influence of histamine, H1 and H2 agonists (2-AETD and dimaprit), and H1 and H2 antagonists (mepyramine and cimetidine) on the postprandial release of pancreatic polypeptide (PP) was assessed in five Labrador retrievers. Infusions of histamine, 0.25 mumol kg-1 h-1; 2AETD, 4 mumol kg-1 h-1; and dimaprit, 1 mumol kg-1 h-1, enhanced postprandial release (131-189% of control values). The response to 2-AETD and dimaprit was significantly different from control values (p less than 0.05). An increase was observed even when 50 mg mepyramine and 400 mg cimetidine were injected as intravenous boluses (131-139% of control values (p less than 0.05]. The action of the antagonists may be explained by partial agonism or histamine release induced by these agents. It is concluded that postprandial PP release is stimulated by H1 and H2 receptors.

Topics: Animals; Cimetidine; Dimaprit; Dogs; Food; Histamine; Histamine H1 Antagonists; Histamine H2 Antagonists; Pancreatic Polypeptide; Pyrilamine; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Secretory Rate; Thiazoles; 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

Dose-response curves of histamine were studied on the mesenteric circulation of the anaesthetized rat. The vasodilation produced by small doses of histamine was prevailingly H2-receptor-dependent, as shown by its inhibition by cimetidine but not by mepyramine, and by its reproducibility by some H2-receptor agonists, but not by specific H1-receptor agonists. The vasodilation produced by high doses of histamine was mainly due to stimulation of H1-receptors, as shown by its 70% inhibition by mepyramine. Mepyramine and cimetidine given simultaneously nearly completely inhibited the vasodilating action of high doses of histamine. Certain H2-receptor agonists, administered at high doses, induced a paradoxical vasoconstriction. It is suggested that a small number of H2-receptors is present in rat mesenteric arterioles, and that these receptors may play a physiological role in the control of mesenteric circulation.

Topics: Animals; Cimetidine; Dimaprit; Rats; Rats, Inbred Strains; Receptors, Histamine; Receptors, Histamine H2; Splanchnic Circulation; Thiazoles; Thiourea; Vasodilation

The effect of histamine (H) and specific H1 and H2 agonists and antagonists on regional myocardial blood flow was studied in anesthetized dogs by use of tracer microspheres. Intracoronary infusion of histamine (15 and 34 micrograms/min) produced a dose-related increase in transmural myocardial blood flow (from 0.82 to 1.36 and 2.25 ml X min-1 X g-1) without alteration of heart rate or blood pressure. Infusion of the H1 agonist 2-(2-thiazolyl)ethylamine (135 and 442 micrograms/min) produced an increase in transmural perfusion (from 0.69 to 1.22 and 1.65 ml X min-1 X g-1) and a significant (P less than 0.05) increase in the ratio of flow between subendocardium and subepicardium (endo/epi from 0.97 to 1.31 and 1.54). Infusion of the H2 agonist dimaprit (195 and 390 micrograms/min) produced an increase in transmural myocardial blood flow (from 0.97 to 1.49 and 2.00 ml X min-1 X g-1) without a change in endo/epi. The H1-mediated increase in regional myocardial perfusion and endo/epi was blocked by the H1 antagonist diphenhydramine but not by the H2 antagonist cimetidine. These results suggest that stimulation of H1 coronary receptors preferentially distributes flow to the subendocardium, whereas H2 receptors mediate vasodilation in subepicardium as well as subendocardium.

Topics: Animals; Blood Pressure; Cimetidine; Coronary Circulation; Dimaprit; Diphenhydramine; Dogs; Female; Heart Rate; Histamine; Male; Microspheres; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Thiazoles; Thiourea