title: An initial characterization of human heart beta-adrenoceptors and their mediation of the positive inotropic effects of catecholamines.
abstract: The positive inotropic effects of catecholamines were studied on samples of ventricular myocardium taken from patients undergoing open heart surgery. The adenylyl cyclase and binding of 3H-(-)-bupranolol were examined in membrane particles prepared from similarly obtained samples. The equilibrium dissociation constant (KD) for (-)-bupranolol was estimated in 4 ways: blockade of the positive inotropic effects of catecholamines, blockade of the stimulation of the adenylyl cyclase by catecholamines, saturation binding of 3H-(-)-bupranolol, inhibition of the binding of 3H-(-)-bupranolol by its unlabeled stereoisomers. The estimates of KD fall in the range 0.5-1.4 nmol/l. The stereo-selectivity ratio (KD (+)-isomer/KD (-)-isomer) is 73. Both values for bupranolol are very similar in cat and man. The inotropic potency of (-)-noradrenaline is nearly 2 orders of magnitude higher in cat heart tissues than in tissues from human hearts. The difference in inotropic potencies between species is only partially accounted for by the five-fold lower potency of (-)-noradrenaline for the human heart adenylyl cyclase as compared to the cat enzyme.
mesh_terms: D000262:Adenylyl Cyclases / Q000032:analysis; D000818:Animals; D002046:Bupranolol / Q000378:metabolism / Q000494:pharmacology; D002395:Catecholamines / Q000494:pharmacology*; D002415:Cats; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism / Q000502:physiology*; D013045:Species Specificity; D013268:Stimulation, Chemical
chemical_list: D002395:Catecholamines; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D002046:Bupranolol; D000262:Adenylyl Cyclases