Differences in beta adrenergic receptor agonist affinity between cardiac myocytes and coronary arterioles in canine heart.

Beta adrenergic receptors (beta AR) are localized in several tissue compartments of the heart, including cardiac myocytes, coronary arteries and coronary arterioles, but it is unclear whether there are differences between tissues in beta AR coupling to G protein. The goal of these studies was to use receptor autoradiography to analyze beta receptor agonist binding characteristics in different tissue compartments of dog heart, including ventricular myocytes (predominantly beta-1) and coronary arterioles (predominantly beta-2). Frozen sections were incubated in [125I]-pindolol with the beta agonist isoproterenol in the absence and presence of 0.1 mM sodium 5'-guanylylimidodiphosphate (GppNHp, a nonhydrolyzable GTP analog) and analyzed by gamma counting or autoradiography. Nonlinear curve-fitting analyses of ventricular section radioactivity indicated that in the absence of GppNHp, the data were consistent with a two-site fit, with 88% of the receptors in the high-affinity state. In autoradiographic analyses, GppNHp displaced the agonist binding curve to a greater extent in arterioles (approximately 100-fold) than in myocytes (approximately 10-fold). This suggests that beta receptors on arterioles are more tightly coupled to G protein than are beta receptors on myocytes. Thus these studies suggest that 1) beta AR on arterioles are coupled more tightly to G protein than are beta AR on myocytes, possibly because of differences in beta receptor subtype, and 2) more beta AR are in the high-affinity state than has been reported previously in more traditional analyses on membrane preparations.