Stimulatory effect of histamine on cyclic AMP formation in chick pineal gland

Histamine (HA) potently stimulated cyclic AMP accumulation in intact pineal glands taken from light-exposed chicks. The action of HA was stronger in the presence of forskolin and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). The effect of HA was mimicked by HA H1- and H2-receptor-selective agonists in the following order of potency: HA > 4-methylhistamine (H2) > 2-methylhistamine (H1) > 2-thiazolylethylamine (H1) >> dimaprit (H2). The HA H3-receptor-selective agonist (R)alpha-methylhistamine was poorly active. The effect of HA was antagonized by selective H2-receptor blockers (tiotidine > oxmetidine > cimetidine = ranitidine) and was not significantly affected by the selective H1- and H3-receptor blockers mepyramine and thioperamide. A detailed analysis of an antagonistic action of ranitidine (versus HA) revealed a noncompetitive mode of action of the H2 blocker. The stimulatory action of the H1 agonist 2-thiazolylethylamine (both under basal conditions and in the presence of forskolin or IBMX) was not significantly influenced by three H1-receptor-selective blockers (mepyramine, triprolidine, and diphenhydramine), but it was totally counteracted by ranitidine. Using accepted selective agonists and antagonists of the HA H1, H2, and H3 receptor we were unable to identify clearly the receptor subtype mediating the HA action on the cyclic AMP-generating system of the chick pineal. It is suggested that the receptor under consideration may represent either an H2-like (in terms of mammalian criteria) or avian-specific HA receptor. The data suggest that HA may be considered a modulator of the pineal activity in chicks.