Evaluation of β1L-Adrenoceptors in Rabbit Heart by Tissue Segment Binding Assay

Abstract.: [3H]-CGP12177 biphasically bound to β-adrenoceptors with high and low affinities in the segments and crude membranes of rabbit left ventricle. The low-affinity sites for [3H]-CGP12177 in the segments was double in density, compared to the density of high-affinity sites. Total abundance of the β-adrenoceptors decreased to approximately 10% upon tissue homogenization, and the proportion of low-affinity sites was the same as that of the high-affinity sites in the membranes. The majority of the high-affinity binding sites of [3H]-CGP12177 in the segments and the membranes were β1H-adrenoceptor, being highly sensitive to propranolol and β1-antagonists (atenolol and ICI-89,406), whereas the low-affinity binding sites showed a β1L-profile (less sensitive to propranolol and β1-, β2-, and β3-antagonists). Furthermore, a part of the β1L-adrenoceptors was insensitive to atenolol, ICI-89,406, and/or isoproterenol. The present binding study clearly shows that β1L-adrenoceptors occur as a distinct phenotype from β1H-adrenoceptors in rabbit ventricle. However, quantitative imbalance between β1H- and β1L-adrenoceptors and divergent ligand–β1L-adrenoceptor interactions suggest a possibility that the β1L-adrenoceptor may not reflect a simple conformational change or allosteric state in the β1-adrenoceptor molecule. Keywords:: β1L-adrenoceptor, β1H-adrenoceptor, CGP12177, rabbit ventricle, tissue segment binding assay