Modulation of cyclic AMP metabolism by protein kinase C in PC18 cells

The present study examined the effect of protein kinase C (PKC) on cyclic AMP metabolism in PC18 cells, a recently developed model of the adrenal medullary chromaffin cell. Activation of PKC with phorbol 12-myristate 13-acetate (PMA) significantly potentiated cAMP accumulation in response to the adenosine analog N⁶-R-phenyl-isopropyl adenosine (PIA) and to forskolin. The degree of potentiation of both PIA and forskolin-stimulated cAMP levels was significantly reduced but not completely eliminated when cells were incubated in the presence of the cAMP-phosphodiesterase (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-dependent cAMP accumulation by PKC in intact PC18 cells is due to both an enhancement of cAMP biosynthetic capacity, as well as a suppression of cAMP catabolic activity.