metiamide and 4-methylhistamine

Histamine and 2-methyl histamine caused dose-dependent aggregation of the integumental melanophores of Rana tigerina both in vitro and in vivo. The aggregating effects were antagonised by mepyramine and metiamide, specific H1 and H2 receptor blockers, respectively. Compound 48/80 and EDTA augmented the melanin-aggregating effects of exogenously applied histamine and 2-methyl histamine in in vivo experiments. 4-Methyl histamine, a specific H2 receptor agonist, dispersed the frog melanophores in in vitro studies, the dispersing effects were blocked by metiamide.

Topics: Animals; Edetic Acid; Histamine; Histamine H1 Antagonists; Histamine H2 Antagonists; In Vitro Techniques; Melanins; Melanophores; Methylhistamines; Metiamide; p-Methoxy-N-methylphenethylamine; Pyrilamine; Ranidae; Receptors, Histamine; Skin; Skin Pigmentation

Histamine and 2-methyl histamine caused dose-dependent aggregation of melanophores in toad B. melanostictus. The effects were effectively antagonised by mepyramine, a specific H1 histamine receptor antagonist, and metiamide a specific H2 receptor antagonist. On the other, hand 4-methyl histamine, a specific H2 receptor agonist dispersed the melanophores. The results suggest that adult Bufo melanophores have H1 histamine receptors which mediate melanophore aggregation, however, dispersion of melanophores may be controlled by undifferentiated histamine receptors of H2 type.

Topics: Animals; Bufonidae; Cell Aggregation; Histamine; Histamine Agents; In Vitro Techniques; Melanophores; Methylhistamines; Metiamide; Pyrilamine

A major site of cerebrospinal fluid production in vertebrates is the choroid plexus. The epithelial cells of the choroid plexus accumulate intracellular cyclic AMP in response to several effectors, including histamine. Since histamine is known to regulate fluid secretion in the stomach via H2 histamine receptors, we asked whether H2 receptors might also be present on epithelial cells of bovine choroid plexus. Using agonists and antagonists of histamine, we show that an agonist and antagonist pair specific for the H2 subtype were clearly more effective than an H1 agonist and antagonist pair in mimicking or inhibiting histamine stimulation of cellular cyclic AMP. Analysis by Schild plot allowed assignment of an apparent dissociation constant to the H2 antagonist metiamide which was 34-fold lower than that of its H1 counterpart, diphenhydramine. These results indicate that epithelial cells of the choroid plexus possess H2 histamine receptors.

Topics: Animals; Cattle; Choroid Plexus; Cyclic AMP; Diphenhydramine; Dose-Response Relationship, Drug; Epithelium; Histamine; Methylhistamines; Metiamide; Receptors, Histamine; Receptors, Histamine H2

Role of histaminergic mechanisms in the regulation of blood-brain barrier (BBB) was assessed in dog. Histamine increased the entry of sodium fluorescein from the blood to the cerebrospinal fluid (CSF) in a dose-dependent manner. Histamine receptor antagonists, mepyramine (H1) and metiamide (H2) per se did not affect the entry of dye in the CSF. Mepyramine failed to affect the change induced by histamine whereas metiamide completely blocked the histamine-induced entry of sodium fluorescein in CSF. 2-Methyl histamine, a specific H1-agonist, did not affect the barrier permeability. However, 4-methyl histamine, a specific H2 receptor agonist significantly increased the permeability of BBB. This increase was blocked by metiamide. Forskolin, a stimulant of adenylate cyclase, also increased the entry of dye in the CSF which could be significantly blocked by metiamide. It is concluded that histamine increases the permeability of BBB by affecting H2-receptors linked to adenylate cyclase.

Topics: Animals; Blood-Brain Barrier; Colforsin; Diterpenes; Dogs; Female; Fluorescein; Fluoresceins; Histamine; Histamine Antagonists; Male; Methylhistamines; Metiamide; Pyrilamine; Time Factors

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

Studies were undertaken to investigate the nature of receptors involved in the prolactin-releasing action of histamine in male rats. The increase of plasma prolactin levels induced by third-ventricle injection of histamine was blocked by intraventricular injection of ranitidine, an H2-antagonist, but not by systemic administration of mepyramine, an H1-antagonist. The H2-histamine agonists 4-methylhistamine and Dimaprit, given intraventricularly in unrestrained and ether-anesthetized rats, enhanced prolactin release. The effect of 4-methylhistamine was dose-dependent, whereas Dimaprit had opposite effects depending on the dose. In low doses, Dimaprit decreased whereas in higher doses it increased plasma prolactin levels. The stimulatory effects of both agonists, similar to those produced by histamine itself, were blocked by metiamide (H2-antagonist), but not by intraventricular mepyramine. High doses of mepyramine only partially decreased the effects of 4-methylhistamine. Ranitidine was able to prevent the prolactin response to 4-methylhistamine. The selective H1-histamine agonist 2,2-pyridylethylamine had no action on prolactin release. 2-Methylhistamine, which exhibits predominantly H1-mediated actions, increased the release of prolactin. Its effect, however, was blocked by low doses of metiamide and was obtained at higher concentrations than 4-methylhistamine. Mepyramine prevented 2-methylhistamine action only at high doses. It is concluded that the increased release of prolactin evoked by histamine in male rats is mainly due to its action on H2-receptors. In addition, the results altogether indicate that H1-receptors have not a significant participation.

Topics: Anesthesia; Animals; Furans; Histamine; Male; Methylhistamines; Metiamide; Prolactin; Pyrilamine; Ranitidine; Rats; Receptors, Histamine

The distribution of histamine receptors was examined in isolated trachealis smooth muscle strips and helical strips of large (5 mm) and small (1.5 mm) intrapulmonary airways. All airways contracted in response to histamine, but the sensitivity to this agent was significantly greater in intrapulmonary airways than in trachealis strips. A dose-dependent tachyphylaxis to histamine occurred when airways were exposed repeatedly to 10(-4) M histamine but not to 5 X 10(-6) M histamine. The H1-agonist, 2-methylhistamine, also caused airway contractions, although they were less forceful than those caused by histamine. Both histamine- and 2-methylhistamine-induced contractions were blocked by the H1-antagonist, pyrilamine. The H2-agonists, 4-methylhistamine and dimaprit, as well as histamine in the presence of pyrilamine failed to relax both acetylcholine- and 5-hydroxytryptamine-induced contractions. Moreover, the H2-antagonist, metiamide, had no effect on histamine-induced contractions. We conclude that histamine H1-receptors are present in both extrapulmonary and intrapulmonary airways of the dog and cause contraction when stimulated. In contrast, histamine H2-receptor activity could not be demonstrated in the airways of this species.

Topics: Animals; Dogs; Dose-Response Relationship, Drug; Electric Stimulation; Histamine; Methylhistamines; Metiamide; Muscle Contraction; Muscle, Smooth; Pyrilamine; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Respiratory System; Tissue Distribution

The mode of action of histamine and its analogues on the secretion of amylase from guinea-pig parotid gland was studied in vitro using chopped parotid tissue. Histamine, 4-methylhistamine and 2-(2-pyridyl)ethylamine dose-dependently stimulated the secretion of amylase in the presence of 3-isobutyl-1-methylxanthine. The effect of histamine was blocked by mepyramine but not by metiamide. Propranolol inhibited the effect of higher concentrations of histamine and 2-(2-pyridyl)ethylamine. A combination of mepyramine and propranolol markedly suppressed the effect of histamine and 2-(2-pyridyl)ethylamine. Atropine, phentolamine and tetrodotoxin had no influence on the histamine-induced secretion of amylase.

Topics: 1-Methyl-3-isobutylxanthine; Amylases; Animals; Atropine; Guinea Pigs; Histamine; In Vitro Techniques; Male; Methylhistamines; Metiamide; Parotid Gland; Propranolol; Pyrilamine; Stimulation, Chemical; Time Factors

Histamine and 4-methylhistamine increased on cyclic AMP level in chopped guinea-pig submandibular glands. 4-Methylhistamine was more active than histamine. 2-(2-Pyridyl)ethylamine was less active than histamine or almost inactive. Metiamide markedly antagonized the histamine-induced cyclic AMP increase but mepyramine had no inhibitory effect on this increase. These results suggest that there are H2-receptors which mediate the cyclic AMP response to histamine in the guinea-pig submandibular gland.

Topics: 1-Methyl-3-isobutylxanthine; Animals; Cyclic AMP; Female; Guinea Pigs; Histamine; Methylhistamines; Metiamide; Pyrilamine; Submandibular Gland

At least wo histamine receptors have been pharmacologically defined. Using the appropriate agonists and antagonists, the possible involvement of these receptor types in the production of reaginic antibodies in the rodent was investigated. After injecting mice with dinitrophenyl-ovalbumin (DNP-OA), maximal serum reaginic titers occurred on day 11 as measured by heterologous passive cutaneous anaphylaxis. If the mice were dosed daily (i.p.) with the H1 agonist, 2-methylhistamine, or the H2 antagonist, metiamide, the titers of reaginic antibodies on day 11 were significantly higher than the controls. The titers were significantly lower than the controls if an H2 agonist (4-methylhistamine, dimaprit, or impromidine) or if the H1 antagonist, pyrilamine, was administered daily. None of these agents significantly affected total serum IgG titers as measured by ELISA. However, if the mice were injected with DNP-OA on day 0, then dosed daily with metiamide, pyrilamine, or 4 methylhistamine beginning on day 32, the titers of reaginic antibodies elicited by a second injection of DNP-OA given on day 36 were not significantly different from the titers of the non-drug treated mice. Thus, under these conditions, with these agents, the results suggest that histamine receptors may be involved in modulating the production of reaginic antibodies during a primary immunological response, H1 receptor agonists enhanced, while H2 receptor agonists suppressed the responses, and the reverse effect was observed with the appropriate antagonists. However, histamine receptors appear not to be measurably involved in the development of the secondary reaginic response.

Topics: Animals; Antibody Formation; Dimaprit; Histamine; Histamine Antagonists; Immunoglobulin E; Male; Methylhistamines; Metiamide; Mice; Reagins; Receptors, Histamine; Thiourea

In this study, we evaluated the effect of histamine on phasic contractile activity in the opossum sphincter of Oddi (SO). SO manometry was done in 35 animals, using an infused catheter system with minimal compliance. In anesthetized animals, phasic SO contractions occurred at a frequency of 7.3 +/- 0.3 (SE) contractions/min with an amplitude of 83 +/- 4 mmHg. Intravenous histamine (5-80 micrograms/kg) invariably inhibited the frequency and amplitude of SO phasic contractions. At larger doses, the SO contractions were abolished for several minutes. The SO inhibitory effect of histamine was duplicated by the selective H1-agonist, 2-pyridylethylamine, and abolished by H1-blockade with pyrilamine or neural blockade with tetrodotoxin. After tetrodotoxin, histamine and 2-pyridylethylamine caused an increased frequency and amplitude of SO contractions. This excitatory effect was blocked by pyrilamine. The histamine effects on SO phasic contractions were not altered by metiamide, atropine, phentolamine, propranolol, hexamethonium, or a large dose of nicotine. We conclude that 1) histamine depresses phasic SO contractions in the opossum; 2) histamine's depressant SO effect is mediated by H1 stimulation of noncholinergic, nonadrenergic SO inhibitory nerves, overriding an H1 stimulatory effect on SO smooth muscle; and 3) histamine has no H2-mediated effect on the opossum SO.

Topics: Ampulla of Vater; Animals; Female; Histamine; Male; Methylhistamines; Metiamide; Motor Activity; Opossums; Pyridines; Pyrilamine; Receptors, Histamine H1; Sphincter of Oddi; Sympatholytics; Tetrodotoxin

The aim of the present research was to evaluate the histaminergic regulation of prolactin secretion in the lactating rat and the possible involvement of H1 and H2 histamine receptors in this control. Prolactin was measured by radioimmunoassay in blood samples withdrawn through an intrajugular silastic catheter from undisturbed lactating mothers 10 to 15 days after delivery. In some of those rats a stainless steel cannula was placed in the third ventricle. The tested drugs, H1 and H2 receptor agonists and antagonists, were injected either by the intrasilastic route or intraventricularly immediately before the onset of suckling and after a basal sample was taken. New samples were withdrawn 10, 20, 30 and 60 min thereafter. Suckling caused a 12- to 18-fold increase in serum prolactin by 10 min in control saline-injected mothers. In non-suckled mothers (NSM) injected with saline, prolactin levels were low at all times. Systemic or intraventricular diphenhydramine and mepyramine, H1 receptor antagonists, suppressed the increment in prolactin observed in suckled mothers (SM). Intraventricular metiamide, an H2 receptor antagonist, did not modify prolactin secretion in SM but drastically increased serum prolactin in NSM. A small but significant increase in prolactin titers was observed in NSM injected intraventricularly with histamine. 4-Methylhistamine, an H2 agonist, was ineffective when used intraventricularly in NSM, but clearly suppressed prolactin enhancement in SM. It is postulated that in lactating mothers, brain histamine has a dual control on prolactin secretion. H2 receptors mediate events related to inhibition of prolactin release, since the agonist 4-methylhistamine blocked the prolactin rise in SM, while the antagonist metiamide promoted release of the hormone in NSM. H1 receptors seem to be related to a facilitatory mechanism since classical antihistamines suppress the serum prolactin increase that follows the onset of suckling, while histamine itself is able to release prolactin in NSM.

Topics: Animals; Diphenhydramine; Female; Histamine; Injections, Intraventricular; Lactation; Methylhistamines; Metiamide; Pregnancy; Prolactin; Rats; Rats, Inbred Strains; Receptors, Histamine H1; Receptors, Histamine H2; Secretory Rate