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 H-1- and H-2-receptor-selective agonists in the following order of potency: HA > 4-methylhistamine (H-2) > 2-methylhistamine (H-1) > 2-thiazolylethylamine (H-1) much greater than dimaprit (H-2) The HA H-3-receptor-selective agonist (R)alpha-methylhistamine was poorly active. The effect of HA was antagonized by selective H-2-receptor blockers (tiotidine > oxmetidine > cimetidine = ranitidine) and was not significantly affected by the selective H-1- and H-3-receptor blockers mepyramine and thioperamide. A detailed analysis of an antagonistic action of ranitidine (versus HA) revealed a noncompetitive mode of action of the H-2 blocker. The stimulatory action of the H-1 agonist 2-thiazolylethylamine (both under basal conditions and in the presence of forskolin or IBMX) was not significantly influenced by three H-1-receptor-selective blockers (mepyramine, triprolidine, and diphenhydramine), but it was totally counteracted by ranitidine. Using accepted selective agonists and antagonists of the HA H-1, H-2, and H-3 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 H-2-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.