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

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Abstract
1 Receptor autoradiography using (—)-[125I]-cyanopindolol (CYP) was used to study the distribution of β-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 × 108 m−1 min−1, K−1 = 1.47 ± 0.25 × 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 β-adrenoceptor subtypes were determined in slide-mounted tissue sections using the antagonists CGP 20712A (β1-selective) and ICI 118,551 (β2-selective). In right atrial appendage and left ventricular papillary muscle 40% (34–45%) of the β-adrenoceptors were of the β2-subtype. 4 Images from X-ray film and nuclear emulsion coated coverslips exposed to (—)-[125I]-CYP-labelled sections showed an even distribution of β-adrenoceptor subtypes over the myocardium of the right atrial appendage, left ventricular papillary muscle and left atrial free wall. Sections of pericardium exhibited predominantly β2-adrenoceptors. β2-Adrenoceptors were localized to the intimal surface of coronary arteries. 5 The selective β1-adrenoceptor agonist R0363 and β2-selective agonist procaterol produced concentration-dependent inotropic responses in right atrial appendage strips. Responses to R0363 were antagonized by CGP 20712A (pKB = 9.29) suggesting an interaction with β,-adrenoceptors. Responses to procaterol were antagonized by ICI 118,551 (pKB = 9.06) suggesting an interaction at β2-adrenoceptors. 6 The finding that a significant proportion of human myocardial adrenoceptors are of the β2-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.