Evaluation of beta1L-adrenoceptors in rabbit heart by tissue segment binding assay.
[(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.
Yoshiki
Hatsumi
H
Division of Pharmacology, Department of Biochemistry and Bioinformative Sciences, School of Medicine, University of Fukui, Fukui, Japan.
Nishimune
Atsushi
A
Suzuki
Fumiko
F
Morishima
Shigeru
S
Ikeda
Takeshi
T
Sasaki
Masato
M
Audigane
Leslie M
LM
Gauthier
Chantal
C
Muramatsu
Ikunobu
I
D000818:Animals; D001665:Binding Sites; D006352:Heart Ventricles / Q000737:chemistry*; D008024:Ligands; D011412:Propanolamines / Q000378:metabolism; D011817:Rabbits; D011869:Radioligand Assay / Q000379:methods*; D018342:Receptors, Adrenergic, beta-1 / Q000032:analysis*
D008024:Ligands; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; C033394:CGP 12177