title: Modulation of cyclic AMP metabolism by protein kinase C in PC18 cells.
abstract: 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 Km 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.
authors.affiliation: Department of Physiology and Biophysics, University of Kentucky, College of Medicine, Lexington 40536-0084.
authors.forename: J D
authors.initials: JD
authors.lastname: Yingling
authors.forename: L Z
authors.initials: LZ
authors.lastname: Fuller
authors.forename: B A
authors.initials: BA
authors.lastname: Jackson
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D005576:Colforsin; D010660:Phenylisopropyladenosine; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D000242:Cyclic AMP; D011493:Protein Kinase C; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D013755:Tetradecanoylphorbol Acetate