title: Okadaic acid increases the phosphorylation state of alpha1A-adrenoceptors and induces receptor desensitization.
abstract: Okadaic acid, a protein phosphatase inhibitor, and phorbol myristate acetate, an activator of protein kinase C, increased the phosphorylation state of alpha1A-adrenergic receptors. The effects of these agents were of similar magnitude but that of okadaic acid developed more slowly. Wortmannin (inhibitor of phosphoinositide 3-kinase), but not staurosporine (inhibitor of protein kinase C), abolished the effect of okadaic acid on the alpha1A-adrenoceptor phosphorylation state. The effect of phorbol myristate acetate on this parameter was blocked by staurosporine and only partially inhibited by wortmannin. Okadaic acid markedly increased the co-immunoprecipitation of both the catalytic and regulatory subunits of phosphatidylinositol 3-kinase and of Akt/protein kinase B with the adrenoceptor and only marginally increases receptor association with protein kinase C epsilon. Okadaic acid induced desensitization of alpha1A-adrenoceptors as evidenced by a decreased ability of noradrenaline to increase intracellular calcium. Such desensitization was fully reverted by wortmannin. Our data indicate that inhibition of serine/threonine protein phosphatases increases the phosphorylation state of alpha1A-adrenergic receptor and alters the adrenoceptor function.
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México. Ap. Postal 70-248, México City 04510, Mexico.
authors.forename: Rocío
authors.initials: R
authors.lastname: Alcántara-Hernández
authors.forename: J Adolfo
authors.initials: JA
authors.lastname: García-Sáinz
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase; D000818:Animals; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019319:Okadaic Acid / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D018340:Receptors, Adrenergic, alpha-1; D019319:Okadaic Acid; D019870:1-Phosphatidylinositol 4-Kinase; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases; D013755:Tetradecanoylphorbol Acetate