Delineation of the Distribution of J-Adrenergic Receptor Subtypes in Canine Myocardium

ft-Receptors constitute only 10-30% of the total 0-adrenergic receptors in mammalian ventricular myocardium, but their precise tissue location cannot be determined easily by measuring physiological variables. To delineate the distribution of /3-receptor subtypes in myocytic and vascular components of the heart, we incubated transmural sections of canine left ventricle with [Iodo]cyanopindolol and selected concentrations of the /3,-selective antagonist betaxolol or the ^-selective antagonist ICI 118,551. Detailed competition binding data were best accounted for by a two-site model in which approximately 75% of total sites were (},and 25% were ft-receptors. The relative proportions of ^-receptor subtypes in myocytic and vascular components were assessed autoradiographically by analyzing the density of binding sites in transmural sections incubated with radioligand and subtype-selective displacers. Betaxolol (10~ M) reduced the density of radioligand binding sites by 44% in regions composed primarily of ventricular myocytes but by <5% in small coronary arterioles. ICI 118,551 (10~ M) reduced radioligand binding-site density by 18% in myocytic regions and by 55% in small arterioles. In myocytic regions, these data indicated a subtype composition of approximately 85% fir and 15% /32-sites. In contrast, arterioles contained almost exclusively the /32-subtype. The diameters of coronary vessels in which /Sj-receptors were found to be selectively increased fell within a narrow range (mean±SD, 35 ± 11 fim; range, 16-55 fim). Small mural arteries and venules did not contain a significantly higher proportion of ft-receptors than adjacent myocytic regions. (Circulation Research 1988;63:117-125)