Xamoterol activates beta 1- but not beta 2-adrenoceptors in mammalian myocardium: comparison of its affinity for beta 1- and beta 2-adrenoceptors coupled to the adenylate cyclase in feline and human ventricle with positive inotropic effects.

The mode of action of xamoterol, a beta 1-selective partial agonist, was investigated in feline myocardium. Xamoterol bound with an 18-fold greater affinity to ventricular beta 1-adrenoceptors (labeled with 3H-bisoprolol) than to beta 2-adrenoceptors (labeled with [3H]ICI 118,551). Xamoterol had a 10-20-fold higher affinity for ventricular beta 1-adrenoceptors coupled to the adenylate cyclase than for cyclase-coupled beta 2-adrenoceptors. The intrinsic activity of xamoterol with respect to (-)-norepinephrine was 0.5 in right ventricular papillary muscles (force), 0.6 in left atria (force); 0.6 in right atria (sinoatrial rate) and 0.1-0.2 in ventricular membranes (cyclase). The stimulant effects of xamoterol were antagonized by beta 1-specific CGP 20,712 A but not by beta 2-selective ICI 118,551. Xamoterol activated only beta 1-adrenoceptors, while beta 2-adrenoceptors occupied by xamoterol remained silent. The positive inotropic effects of a nearly maximally effective xamoterol concentration were associated with a considerably greater beta 1-mediated cyclase stimulation than the same inotropic effect of (-)-norepinephrine. In human ventricular membranes xamoterol stimulated marginally the adenylate cyclase and antagonized the effects of (-)-norepinephrine with a 30-fold greater affinity for beta 1- than for beta 2-adrenoceptors.