The human heart beta-adrenergic receptors. II. Coupling of beta 2-adrenergic receptors with the adenylate cyclase system.

The beta-adrenergic stimulation of adenylate cyclase in membranes from human auricles, ventricles, and fetal heart was compared with the binding properties of beta-adrenergic receptors in human auricles. In terms of adenylate cyclase activation, three full agonists (isoproterenol, epinephrine, and norepinephrine), four partial agonists (procaterol, salbutamol, fenoterol, and zinterol), and four antagonists (propranolol, metoprolol, atenolol, and practolol) were tested. The beta-adrenergic activation of adenylate cyclase in membranes from rat heart (with a majority of beta 1-adrenergic receptors), rat erythrocytes, and rat reticulocytes (with a homogeneous population of beta 2-adrenergic receptors) served as reference. The reactivity of human heart adenylate cyclase, estimated by the Kact or Ki values of 11 beta-adrenergic agents, indicated that the activation of this enzyme occurred through receptors of the beta 2-subtype only. Receptors of the beta 1-subtype (50% of the total population) were not coupled to the enzyme.