DOES HISTAMINE STIMULATE CYCLIC-AMP FORMATION IN THE AVIAN PINEAL-GLAND VIA A NOVEL (NON-H-1, NON-H-2, NON-H-3) HISTAMINE-RECEPTOR SUBTYPE

The effects of histamine (HA), and selective HA H-1-, H-2 and H-3-rece ptor agonists on cyclic AMP formation were investigated in intact chic k and duck pineal glands. HA potently stimulated the pineal cyclic AMP formation. The effect of KA was mimicked fully by N alpha-methylated histamines, and partially by several histaminergic drugs: 2-thiazolyle thylamine (H-1), amthamine (H-2) and R alpha-methylhistamine (H-3). Di maprit, another selective H-2-agonist showed marginal activity. Forsko lin highly potentiated the action of HA, and only weakly affected the effects of 2-thiazolylethylamine and amthamine. In the chick pineal, t he stimulatory effects of HA and the tested histaminergic drugs were n ot blocked by mepyramine and thioperamide (H-1- and H-3-blockers, resp ectively), but they were antagonized by H-2-receptor selective compoun ds ranitidine and aminopotentidine, which, however, acted in a noncomp etitive manner. Another H-2-selective blocker zolantidine antagonized the HA effect only when used at very high (30-100 mu M) concentrations . In the duck pineal, the stimulatory effect of HA on cyclic AMP produ ction was unaffected by mepyramine (H-1), thioperamide (H-3), and rani tidine (H-2), and only partially inhibited by the H-2-blocker aminopot entidine. Electrophysiological experiments revealed that HA is capable of evoking inward currents in most of the tested cells acutely isolat ed from chick pineal gland. The present findings further indicate that the pharmacological profile of the avian pineal HA receptor, whose st imulation leads to activation of cyclic AMP production, is different f rom any known HA receptor type (H-1, H-2, H-3), and suggest the existe nce of either an avian-specific HA receptor, or a novel HA receptor su btype. Electrophysiological data suggest that the pineal KA receptor m ay be somehow linked to activation of an ionic channel.