Does histamine stimulate cyclic amp formation in the avian pineal gland via a novel (non-H1, non-H2, non-H3) histamine receptor subtype

Abstract The effects of histamine (HA), and selective HA, H 1 -, H 2 and H 3 -receptor agonists on cyclic AMP formation were investigated in intact thick and duck pineal glands. HA potently stimulated the pineal cyclic AMP formation. The effect of HA was mimicked fully by Nα - methylated histamines, and partially by several histaminergic drugs: 2-thiazolylethylamine (H 1 ), amthamine (H 2 ) and Rα - methylhistamine (H 3 ). Dimaprit, another selective H 2 -agonist showed marginal activity. Forskolin highly potentiated the action of HA, and only weakly affected the effects of 2-thiazolyethylamine and amthamine. In the chick pineal, the stimulatory effects of HA and the tested histaminergic drugs were not blocked by mepyramine and thioperamide (H 1 - and H 3 -blockers, respectively), but they were antagonized by H 2 -receptor selective compounds ranitidine and aminopotentidine, which, however, acted in a noncompetitive manner. Another H 2 -selective blocker zolantidine antagonized the HA effect only when used at very high (30–100 μM) concentrations. In the duck pineal, the stimulatory effect of HA on cyclic AMP production was unaffected by mepyramine (H 1 ), thioperamide (H 3 ), and ranitidine (H 2 ), and only partially inhibited by the H 2 -blocker aminopotentidine. Electrophysiological experiments revealed that HA is capable of evoking inward currents in most of the tested cells acutely isolated from chick pineal gland. The present findings further indicate that the pharmacological profile of the avian pineal HA receptor, whose stimulation leads to activation of cyclic AMP production, is different from any known HA receptor type (H 1 , H 2 , H 3 ), and suggest the existence of either an avian-specific HA receptor, or a novel HA receptor subtype. Electrophysiological data suggest that the pineal HA receptor may be somehow linked to activation of an ionic channel.