Differential involvement of PKA and PKC in regulation of catecholamine enzyme genes by PACAP.
Roles of protein kinase A (PKA) and protein kinase C (PKC) in regulation of tyrosine hydroxylase, dopamine beta-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 beta-hydroxylase activities, but slightly lowered phenylethanolamine N-methyltransferase activity, resulting in a preferential rise in norepinephrine over epinephrine.
Choi
H J
HJ
Department of Biochemistry, University of Ulsan College of Medicine, Seoul, Korea.
Park
S Y
SY
Hwang
O
O
D000818:Animals; D002395:Catecholamines / Q000096:biosynthesis*; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004299:Dopamine beta-Hydroxylase / Q000235:genetics / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D009479:Neuropeptides / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D010625:Phenylethanolamine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
D002395:Catecholamines; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D010625:Phenylethanolamine N-Methyltransferase; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D009638:Norepinephrine; D004837:Epinephrine