Roles of protein kinase A (PKA) and protein kinase C (PKC) in regulation of tyrosine hydroxylase, dopamine β-hydroxylase, and phenylethanolamine N-methyltransferase expression by pituitary adenylate cyclase-activating polypeptide (PACAP) were determined in primary cultured bovine chromaffin cells. DBH up-regulation by PACAP was reduced by H-89 and not further increased by forskolin showing involvement of cAMP/PKA. It was not mediated by PKC, as 12- O-tetradecanoylphorbol-13-acetate and sphingosine exerted no effect. Tyrosine hydroxylase induction by PACAP was mediated by both kinases. The PACAP-activated PKA up-regulated phenylethanolamine N-methyltransferase expression whereas PKC caused down-regulation. PACAP increased tyrosine hydroxylase and dopamine β-hydroxylase activities, but slightly lowered phenylethanolamine N-methyltransferase activity, resulting in a preferential rise in norepinephrine over epinephrine .