An initial characterization of human heart beta-adrenoceptors and their mediation of the positive inotropic effects of catecholamines.
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.
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
D002395:Catecholamines; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D002046:Bupranolol; D000262:Adenylyl Cyclases