title: Regulation of cyclic AMP levels by phorbol esters in bovine adrenal medullary cells.
abstract: Cyclic AMP responses to phorbol esters were studied in cultured bovine adrenal medullary cells. Phorbol esters that activate protein kinase C (PKC: phorbol 12,13-dibutyrate, phorbol 12,13-didecanoate) increased cellular cyclic AMP levels by up to 100% over 5 min, and this was maintained for up to 3 h. The effect was mimicked by 1,2-dioctanoyl-sn-glycerol but not by inactive phorbol esters. The effect of active phorbol esters was concentration dependent over the range 50-500 nM, and was abolished by the PKC inhibitor, Ro 31-8220 (10 microM). The response was enhanced by 3-isobutyl-1-methylxanthine (1 mM) and by forskolin (0.3 microM), was enhanced following pertussis toxin pretreatment (100 ng/ml, 7.5 h) and was unaffected by removing extracellular Ca2+. The phorbol ester cyclic AMP response was additive with that to K+ depolarisation, and synergised with those to prostaglandin E1 and dimaprit. The results indicate PKC activation increases cyclic AMP formation in bovine adrenal medullary cells, probably by a direct action on adenylate cyclase or Gs.
authors.affiliation: Department of Biochemistry, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: P D
authors.initials: PD
authors.lastname: Marley
authors.forename: K A
authors.initials: KA
authors.lastname: Thomson
authors.forename: K
authors.initials: K
authors.lastname: Hoy
authors.forename: P
authors.initials: P
authors.lastname: Maccarone
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D037361:Adenylate Cyclase Toxin; D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004075:Diglycerides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D007211:Indoles / Q000494:pharmacology; D037342:Pertussis Toxin; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D037361:Adenylate Cyclase Toxin; D004075:Diglycerides; D007211:Indoles; D010703:Phorbol Esters; D010566:Virulence Factors, Bordetella; C044295:1,2-dioctanoylglycerol; D005576:Colforsin; C008876:phorbol-12,13-didecanoate; D015240:Phorbol 12,13-Dibutyrate; D000242:Cyclic AMP; D037342:Pertussis Toxin; D011493:Protein Kinase C; D015056:1-Methyl-3-isobutylxanthine; C064758:Ro 31-8220