Heart ß-Receptors: On the Functional Role of Heterogeneous Binding Sites

Abstract

ß-Receptor subtypes were studied in the myocardium of reserpine-pretreated kittens. Membrane particles were prepared from dispersed ventricular cells. Binding of ³H-(−)-propranolol to membranes revealed saturable characteristics of a single class of complex (K_D 2.5 nmol/1). The agonist procaterol exhibited 2 binding components with K_D's of 2.5 and 20000 nmol/1; ¼ of the sites has high-affinity characteristics. Procaterol stimulated the adenylyl cyclase (intrinsic activity 0.5 compared to (−)-isoprenaline); the effect was competitively antagonized by ß-blockers. Procaterol caused biphasic concentration-effect curves for the cyclase; a high-affinity component of the curve comprised 60-70% of the maximum enzyme stimulation by procaterol. Inotropic concentration-effect curves for procaterol were also biphasic on isolated papillary muscles and left atria; procaterol was a full inotropic agonist and the high-affinity component of the curve amounted to 30-40% of the maximal effect. The rate of spontaneously beating right atria was enhanced by procaterol with a 1000-fold higher potency than for inotropic effects; the chronotropic concentration-effect curve was monophasic. The positive chronotropic and inotropic effects of procaterol were competitively antagonized by ß-blockers. Both procaterol sites appear to mediate its positive inotropic effects. The high-affinity procaterol sites appear to encounter preferentially the adenylyl cyclase but the formed cAMP may be used less efficiently for inotropism than the cAMP formed from the low-affinity site. Procaterol may stimulate the beating rate of sinoatrial pacemakers predominantly through its high-affinity sites.