title: Protein phosphatase-protein kinase interplay modulates alpha 1b-adrenoceptor phosphorylation: effects of okadaic acid.
abstract: In the present work we studied the effect of protein phosphatase inhibitors on the phosphorylation state and function of alpha(1b)-adrenoceptors. Okadaic acid increased receptor phosphorylation in a time- and concentration-dependent fashion (maximum at 30 min, EC(50) of 30 nM). Other inhibitors of protein phosphatases (calyculin A, tautomycin and cypermethrin) mimicked this effect. Staurosporine and Ro 31-8220, inhibitors of protein kinase C, blocked the effect of okadaic acid on receptor phosphorylation. Neither genistein nor wortmannin altered the effect of okadaic acid. The intense adrenoceptor phosphorylation induced by okadaic acid altered the adrenoceptor-G protein coupling, as evidenced by a small decreased noradrenaline-stimulated [(35)S]GTPgammaS binding. Okadaic acid did not alter the noradrenaline-stimulated increases in intracellular calcium or the production of inositol trisphosphate. Our data indicate that inhibition of protein phosphatases increases the phosphorylation state of alpha(1b)-adrenoceptors; this effect seems to involve protein kinase C. In spite of inducing an intense receptor phosphorylation, okadaic acid alters alpha(1b)-adrenergic actions to a much lesser extent than the direct activation of protein kinase C by phorbol myristate acetate.
authors.affiliation: Instituto de Fisiologia Celular, Universidad Nacional Autonoma de Mexico. Ap. postal 70-248.
authors.forename: R
authors.initials: R
authors.lastname: Alcántara-Hernández
authors.forename: J
authors.initials: J
authors.lastname: Vázquez-Prado
authors.forename: J A
authors.initials: JA
authors.lastname: Gárcia-Sáinz
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D008387:Marine Toxins; D019319:Okadaic Acid / Q000494:pharmacology*; D010080:Oxazoles / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D011714:Pyrans; D011722:Pyrethrins / Q000494:pharmacology; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism* / Q000502:physiology; D013141:Spiro Compounds; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D007211:Indoles; D008387:Marine Toxins; D010080:Oxazoles; D011714:Pyrans; D011722:Pyrethrins; D018340:Receptors, Adrenergic, alpha-1; D013141:Spiro Compounds; C053079:tautomycin; C017160:cypermethrin; D019319:Okadaic Acid; C059041:calyculin A; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; C064758:Ro 31-8220