HISTAMINE-STIMULATED CYCLIC-AMP FORMATION IN THE CHICK PINEAL-GLAND -ROLE OF PROTEIN-KINASE-C

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.