title: Characterization of stimulation of phosphoinositide hydrolysis by alpha 1-adrenergic agonists in adult rat hearts.
abstract: The coupling of the pharmacologically defined alpha 1A- and alpha 1B-adrenoceptors to the hydrolysis of phospho[3H]inositides (PI) was investigated in ventricular myocytes freshly isolated from adult rat hearts. The alpha 1-adrenoceptor population in the heart was characterized by competitive binding experiments using [3H]prazosin and the alpha 1A-adrenoceptor-selective antagonist 5-methyl urapidil. It was heterogeneous with approximately 25% being pharmacologically of the alpha 1A-adrenoceptor subtype and 75% being of the alpha 1B-adrenoceptor subtype. Epinephrine, norepinephrine, or phenylephrine stimulated PI hydrolysis in the presence or absence of propranolol. The greatest stimulation (7-fold) was with epinephrine. The half-maximum effective concentrations for agonists were approximately 0.5-3.5 and 0.2 microM in the absence and presence of propranolol, respectively. The inhibition by 5-methyl urapidil of the stimulation of PI hydrolysis by a fixed concentration of epinephrine fitted a two-site competition curve. The distribution between high-affinity (25%) and low-affinity (75%) sites suggested that both the alpha 1A- and alpha 1B-adrenoceptors were coupled to PI hydrolysis in proportion to their relative abundance. Equally, the stimulation of PI hydrolysis by epinephrine in the presence of a fixed concentration of 5-methyl urapidil was biphasic. In addition, chloroethylclonidine, an irreversible inhibitor of the alpha 1B-adrenoceptor, inhibited the epinephrine stimulation of PI hydrolysis by 35%. We conclude that the pharmacologically defined alpha 1A- and alpha 1B-adrenoceptor subtypes are both coupled to PI hydrolysis in the ventricular myocyte.
authors.affiliation: Department of Cardiac Medicine, National Heart and Lung Institute, University of London, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Lazou
authors.forename: S J
authors.initials: SJ
authors.lastname: Fuller
authors.forename: M A
authors.initials: MA
authors.lastname: Bogoyevitch
authors.forename: K A
authors.initials: KA
authors.lastname: Orfali
authors.forename: P H
authors.initials: PH
authors.lastname: Sugden
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004837:Epinephrine / Q000494:pharmacology; D006352:Heart Ventricles; D006868:Hydrolysis / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014649:Vas Deferens / Q000378:metabolism
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D010716:Phosphatidylinositols; D010656:Phenylephrine; D009638:Norepinephrine; D004837:Epinephrine