| Title | Evaluation of beta(1L)-Adrenoceptors in Rabbit Heart by Tissue Segment Binding Assay. | | Author(s) | Yoshiki H, Nishimune A, Suzuki F, Morishima S, Ikeda T, Sasaki M, Audigane LM, Gauthier C, Muramatsu I | | Institution | Division of Pharmacology, Department of Biochemistry and Bioinformative Sciences, School of Medicine, University of Fukui, Japan. | | Source | J Pharmacol Sci 2009 Jul 3. | | Abstract | [(3)H]-CGP12177 biphasically bound to beta-adrenoceptors with high and low affinities in the segments and crude membranes of rabbit left ventricle. The low-affinity sites for [(3)H]-CGP12177 in the segments was double in density, compared to the density of high-affinity sites. Total abundance of the beta-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 [(3)H]-CGP12177 in the segments and the membranes were beta(1H)-adrenoceptor, being highly sensitive to propranolol and beta(1)-antagonists (atenolol and ICI-89,406), whereas the low-affinity binding sites showed a beta(1L)-profile (less sensitive to propranolol and beta(1)-, beta(2)-, and beta(3)-antagonists). Furthermore, a part of the beta(1L)-adrenoceptors was insensitive to atenolol, ICI-89,406, and/or isoproterenol. The present binding study clearly shows that beta(1L)-adrenoceptors occur as a distinct phenotype from beta(1H)-adrenoceptors in rabbit ventricle. However, quantitative imbalance between beta(1H)- and beta(1L)-adrenoceptors and divergent ligand-beta(1L)-adrenoceptor interactions suggest a possibility that the beta(1L)-adrenoceptor may not reflect a simple conformational change or allosteric state in the beta(1)-adrenoceptor molecule. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19574725 |
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