Jb. Zawilska et al., HISTAMINE-STIMULATED CYCLIC-AMP FORMATION IN THE CHICK PINEAL-GLAND -ROLE OF PROTEIN-KINASE-C, Biochemical pharmacology, 54(4), 1997, pp. 501-507
The role of protein kinase C (PKC) in histamine (HA)-stimulated cyclic
AMP formation in intact chick pineal glands was investigated. In the
pineal gland of chick HA, 2-methylHA, 4-methylHA, and N alpha,N alpha-
dimethylHA potently increased cyclic AMP accumulation in a concentrati
on-dependent manner. Treatment of intact glands with PKC inhibitors, i
.e. chelerythrine and staurosporine, reduced the stimulatory effect of
the HA-ergic compounds on cyclic AMP formation. HA, 2-methylHA, 4-met
hylHA, and N alpha,N alpha-dimethylHA significantly increased inositol
-1,4,5-trisphosphate (IP3) levels in intact chick pineal glands, indic
ating their activities on phospholipase C and 1,2-diacylglycerol forma
tion. The stimulatory effect of HA on IP3 levels was antagonized by am
inopotentidine, a potent blocker of H-2-like HA receptors in avian pin
eal gland. Preincubation of chick pineal glands with a PKC activator,
4 beta-phorbol 12,13-dibutyrate (4 beta-PDB), enhanced the accumulatio
n of cyclic AMP elicited by HA, 2-methylHA, 4-methylHA, and N alpha,N
alpha-dimethylHA. On the other hand, 4 beta-phorbol, inactive on the P
KC, was ineffective. Our results point to the possibility that PKC is
involved in the regulation by HA of cyclic AMP synthesis in the pineal
gland of chick. Furthermore, the cyclic AMP response to pineal HA rec
eptor stimulation can be positively modulated by a concomitant activat
ion of the PKC pathway. (C) 1997 Elsevier Science Inc.