Different changes of plasma membrane β-adrenoceptors in rat heart after chronic administration of propranolol, atenolol and bevantolol

Recently, tissue segment binding method with a hydrophilic radioligand [3H]-CGP12177 was developed to detect plasma membrane β-adrenoceptors in rat heart (Horinouchi et al., 2006). In the present study, propranolol (40 mg kg− 1 day− 1), atenolol (40 mg kg− 1 day− 1) and bevantolol (200 mg kg− 1 day− 1) were administered to rats for 6 weeks, and the changes of plasma membrane β-adrenoceptors and their mRNA expression in rat ventricle were examined. Chronic administration of propranolol increased the β1-adrenoceptors but decreased the β2-adrenoceptors without changing total amount of plasma membrane β-adrenoceptors. Atenolol increased both plasma membrane β1- and β2-adrenoceptors, whereas bevantolol had no effect on the β-adrenoceptor density and their subtype proportions. In contrast, the density of β-adrenoceptors detected in conventional homogenate binding study was extremely low (approximately 60% of plasma membrane β-adrenoceptors detected with the tissue segment binding method) and the effects of chronic administration of β-adrenoceptor antagonists were not necessarily in accord with those at the plasma membrane β-adrenoceptors. The mRNA levels of β1- and β2-adrenoceptors were not altered by propranolol treatment, while β1-adrenoceptor mRNA significantly decreased after administration of atenolol or bevantolol without changing the level of β2-adrenoceptor mRNA. The present binding study with intact tissue segments clearly shows that the plasma membrane β1- and β2-adrenoceptors of rat heart, in contrast to the homogenate binding sites and the mRNA levels, are differently affected by chronic treatment with three β-adrenoceptor antagonists; up- and down-regulations of β1- and β2-adrenoceptors, respectively, by propranolol, and up-regulation of both the subtypes by atenolol, but no significant change in both the subtypes by bevantolol.