Characterization and autoradiographic localization of β‐adrenoceptor subtypes in human cardiac tissues

1 Receptor autoradiography using (-)-125I-cyanopindolol (CYP) was used to study the distribution of beta-adrenoceptor subtypes in human right atrial appendage, left atrial free wall, left ventricular papillary muscle and pericardium. 2 The binding of (-)-125I-CYP to slide-mounted tissue sections of human right atrial appendage was time-dependent (K1 = 4.11 +/- 1.01 X 10(8) M-1 min-1, K-1 = 1.47 +/- 0.25 X 10(-3) min-1, n = 3), saturable (42.02 +/- 2.96 pM, n = 4) and stereoselective with respect to the optical isomers of propranolol (pKD (-):8.97 +/- 0.02, (+):6.88 +/- 0.06, n = 3). 3 The proportions of beta-adrenoceptor subtypes were determined in slide-mounted tissue sections using the antagonists CGP 20712A (beta 1-selective) and ICI 118,551 (beta 2-selective). In right atrial appendage and left ventricular papillary muscle 40% (34-45%) of the beta-adrenoceptors were of the beta 2-subtype. 4 Images from X-ray film and nuclear emulsion coated coverslips exposed to (-)-125I-CYP-labelled sections showed an even distribution of beta-adrenoceptor subtypes over the myocardium of the right atrial appendage, left ventricular papillary muscle and left atrial free wall. Sections of pericardium exhibited predominantly beta 2-adrenoceptors. beta 2-Adrenoceptors were localized to the intimal surface of coronary arteries. 5 The selective beta 1-adrenoceptor agonist RO363 and beta 2-selective agonist procaterol produced concentration-dependent inotropic responses in right atrial appendage strips. Responses to RO363 were antagonized by CGP 20712A (pKB = 9.29) suggesting an interaction with beta 1-adrenoceptors. Responses to procaterol were antagonized by ICI 118,551 (pKB = 9.06) suggesting an interaction at beta 2-adrenoceptors. 6 The finding that a significant proportion of human myocardial adrenoceptors are of the beta 2-subtype has important clinical implications for the involvement of these receptors in the control of heart rate and force, and the autoradiographic evidence suggests other roles in the coronary vasculature and pericardium.