Stimulatory Effect of Histamine on Cyclic AMP Formation in Chick Pineal Gland

Abstract: 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)α-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.