metiamide and 2-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

Topics: Animals; Dose-Response Relationship, Drug; Histamine; In Vitro Techniques; Methylhistamines; Metiamide; Muscle, Smooth; Omasum; Sheep

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

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

Topics: Animals; Blood Pressure; Cats; Dimaprit; Electric Stimulation; Female; Histamine; Histamine Antagonists; Hypothalamus; Male; Methylhistamines; Metiamide; Sympathomimetics; Thiourea; Time Factors