Role of alpha1-adrenoceptor subtypes in production of the positive inotropic effects in mammalian myocardium: implications for the alpha1-adrenoceptor subtype distribution.
Both alpha1A- and alpha1B-adrenoceptor subtypes are present in mammalian myocardium. Alpha1-adrenoceptor activation can enhance myocardial contractility, and two possible inotropic mechanisms are proposed: an increase in myofilament Ca2+ sensitivity and an increase in transsarcolemmal Ca2+ influx during action potential prolongation that accompanies the transient outward current inhibition. We suggest that the former is mediated by the alpha1B-adrenoceptor subtype and the latter is by the alpha1A-adrenoceptor subtype. The alpha1B-adrenoceptor subtype may be located on a space more proximal to the sympathetic nerve endings than the alpha1A-adrenoceptor subtype, because the positive inotropic effect of endogenous norepinephrine was mediated entirely by the alpha1B-adrenoceptor subtype. In some species, the sustained positive inotropic effect develops following the transient negative inotropic effect, which is mediated by the alpha1A-adrenoceptor subtype.
Hattori
Y
Y
Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
Kanno
M
M
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology*; D009206:Myocardium / Q000648:ultrastructure*; D010656:Phenylephrine / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification* / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D002316:Cardiotonic Agents; D004146:Dioxanes; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane