title: Phorbol-12,13-dibutyrate antagonizes the alpha 1-adrenoceptor-mediated positive inotropic effect in the rabbit ventricular myocardium.
abstract: The phorbol ester phorbol-12,13-dibutyrate (PDBu) elicited a slight but significant positive inotropic effect (PIE) (10-100 nM) in the presence of a beta-adrenoceptor antagonist (+/-)-bupranolol (300 nM). PDBu (10-1000 nM) inhibited the alpha 1-adrenoceptor mediated PIE in a concentration-dependent manner, while beta-adrenoceptor-mediated PIE was not decreased by PDBu up to 300 nM. Thus, PDBu exerted a differential effect on alpha- and beta-adrenoceptor-mediated PIE, and was much more effective than 12-O-tetradecanoylphorbol-13-acetate (TPA) in antagonizing the alpha-adrenoceptor-mediated PIE. These findings imply that (1) certain subcellular process of myocardial alpha-adrenoceptor stimulation may be specifically antagonized by an activation of protein kinase C induced by PDBu or TPA; (2) there may be species difference in the response to activation of protein kinase C, which results in differential modulation of myocardial alpha 1-adrenoceptor-mediated regulation of contractility among different mammalian species.
authors.affiliation: Department of Pharmacology, Yamagata University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Endoh
authors.forename: J
authors.initials: J
authors.lastname: Otomo
authors.forename: I
authors.initials: I
authors.lastname: Norota
mesh_terms: D000317:Adrenergic alpha-Antagonists; D000818:Animals; D006352:Heart Ventricles / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D000317:Adrenergic alpha-Antagonists; D010656:Phenylephrine; D015240:Phorbol 12,13-Dibutyrate