Jz. Nowak et al., 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, Neurochemistry international, 27(6), 1995, pp. 519-526
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.