Binding characteristics of 125I-iodocyanopindolol to beta-adrenergic receptors: biphasic Scatchard plots. II. Effects of selective antagonists.

Abstract

The characteristics of the high-and low-affinity binding sites for 125I-iodocyanopindolol (125I-ICYP) in rat cerebral cortex membrane were examined. The Scatchard plots of 125I-ICYP binding were biphasic in the absence of antagonists as well as in the presence of non-selective antagonists (d-, dl- and l-propranolol) and selective antagonists. Two of the latter (atenolol and practolol) are β1-selective antagonists and two others (butoxamine and ICI-118551) are β2-selective antagonists.The β2-selective antagonists showed more potent action on the high-affinity sites than on the low-affinity sites, while the β1-selective antagonists had a more potent effect on the low-affinity sites. These results were consistent with those obtained from pharmacological experiments, and suggest that the high- and low-affinity sites in the biphasic Scatchard plots correspond to β2-and β1-adrenoceptors, respectively.By means of this approach, the relative percentages of the two receptor subtypes in rat brain (cerebral cortex), lung, heart, and spleen were calculated (ratios of β1 : β2-adrenoceptors) to be brain 89 : 11, lung 28 : 72, heart 92 : 8, and spleen 59 : 41. The absolute capacities of β-adrenoceptors per g wet weight in these tissues were 10-14 pmol/g tissue except for heart (approx. 2.4 pmol/g tissue).