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.

Histamine H2‐like receptors in chick cerebral cortex: effects on cyclic AMP synthesis and characterization by [3H]tiotidine binding

“…This tissue is less sensitive to the studied action of HA than chick (and also duck) pineal gland, but clearly more sensitive than the cerebral cortex of mammals, such as guinea pigs and rabbits (Daly et al . 1982; Al‐Gadi and Hill 1985; Gannon and Hough 1988; Nowak and Sek 1994; Nowak et al . 1995a,b).…”

“…1982; Sek et al . 1988; Nowak 1993; Nowak and Sek 1994), the action of HA was strongly potentiated by forskolin, a direct activator of adenylyl cyclase (Seamon and Daly 1986), suggesting a likely receptor‐related mode of action for HA. The action of HA in the chick cerebral cortex seems to be specific in that several HA‐like compounds, i.e.…”

“…We have previously demonstrated that HA is a powerful stimulator of cAMP production in intact pineal glands of domestic fowls, i.e. hens, ducks, and geese; the amine did not, however, affect the nucleotide formation in the rat pineal gland (Nowak and Sek 1994; Nowak et al . 1995a,b, 1998).…”

“…The action of HA was mediated by a specific receptor, whose pharmacological profile is different from that of the H 1 , H 2 , H 3 and H 4 subtypes of HA receptor described for mammalian tissues. It has been suggested that this pineal HA receptor represents either an avian‐specific H 2 ‐like receptor or a novel HA receptor subtype (Nowak and Sek 1994; Nowak et al . 1995a,b).…”

Pharmacological properties and SAR of new 1,4-disubstituted piperazine derivatives with hypnotic-sedative activity

“…Assay of cyclic AMP formation was carried out by the method described in detail by Nowak & Sek (1994) on rat striatum and cerebral cortex. Some experiments were carried out on guinea-pig cerebral cortex tissue.…”