Regulation of basal expression of catecholamine-synthesizing enzyme genes by PACAP

We have previously reported that the cAMP/protein kinase A (PKA) pathway is important in the gene regulation of both induction and basal expressions o f the catecholamine synthesizing enzymes tyrosine hydroxylase (TH) and dopa mine P-hydroxylase (DBH). The neuropeptide pituitary adenylate cyclase acti vating polypeptide (PACAP) has been shown to activate the intracellular cAM P/PKA pathway. In the present study, using primary cultured bovine adrenal medullary cells, we determined whether the basal activity of the PACAP rece ptor might play a role in the maintenance of the basal expression of these enzyme genes via the cAMP/ PKA pathway. The potent PACAP receptor antagonis t PACAP (6-38) caused a reduction of TH and DBH mRNA levels in a dose depen dent manner as well as their enzyme activities and TH protein level. The ef fects of PACAP (6-38) and the PKA inhibitor H-89 exhibited generally simila r trends, and were not additive in the reduction of TH and DBH gene express ion and activities, suggesting that they take a common intracellular signal ing pathway. The antagonist also caused decreases in the intracellular nore pinephrine and epinephrine levels similar to the effect of H-89, Taken toge ther, the data suggests that PACAP is involved in the regulation of mainten ance of the catecholamine synthesizing enzymes TH and DBH by utilizing the cAMP/PKA pathway.