metiamide and 2-(2-aminoethyl)pyridine

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, 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

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

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 (H) and H1 agonists 2-pyridylethylamine (PEA) and 2-methylhistamine (2-MH) produced a greater depression of the corticospinal and unidentified rat cerebral cortical neurones than did 4-methylhistamine (4-MH), an H2 agonist. Mepyramine antagonized the effects of 2-MH, PEA and H, and partially antagonized the depression induced by 4-MH. Metiamide and cimetidine, H2 antagonists, blocked 4-MH and H but not 2-MH- and PEA-induced depression. These results indicate that H-induced depression of cortical neurones involves activation of H1 and H2 receptors.

Topics: Acetylcholine; Animals; Cerebral Cortex; Guanidines; Histamine; Imidazoles; In Vitro Techniques; Male; Metiamide; Neurons; Norepinephrine; Pyridines; Pyrilamine; Rats; Receptors, Drug