MODULATION OF CYCLIC-AMP METABOLISM BY PROTEIN-KINASE-C IN PC18 CELLS

The present study examined the effect of protein kinase C (PKC) on cyc lic AMP metabolism in PC18 cells, a recently developed model of the ad renal medullary chromaffin cell. Activation of PKC with phorbol 12-myr istate 13-acetate (PMA) significantly potentiated cAMP accumulation in response to the adenosine analog N-6-R-phenyl-isopropyl adenosine (PI A) and to forskolin. The degree of potentiation of both PIA and forsko lin-stimulated cAMP levels was significantly reduced but not completel y eliminated when cells were incubated in the presence of the cAMP-pho sphodiesterase (cAMP-PDE) inhibitor Ro20-1724. PMA pretreatment had no detectable effect on either cytosolic or membrane-bound low K-m cAMP- PDE activity, but did significantly potentiate PIA-dependent adenylate cyclase activity. We conclude that the potentiation of agonist-depend ent cAMP accumulation by PKC in intact PC18 cells is due to both an en hancement of cAMP biosynthetic capacity, as well as a suppression of c AMP catabolic activity.