The selectivities, potencies and efficacies of β3-adrenoceptor (β3-AR) agonists on human three β-AR subtypes expressed in Chinese hamster ovary (CHO) cells were investigated using radioligand binding assay and cyclic AMP (cAMP) accumulation assay. The three β-AR subtypes showed the nature of G protein-coupled receptors with the constitutive activity. BRL37344, CL-316,243 and a newly synthesized β3-AR agonist N-5984, 6-[2-(R)-[ [2-(R)-(3-chlorophenyl)-2-hydroxyethyl] amino ] propyl ]-2, 3-dihydro-1, 4-benzodioxine-2-(R)-carboxylic acid, were compared for the potency and selectivity for the β3-AR. In the radioligand binding assay, the affinity of N-5984 for β3-ARs was 14, 70 and 220 times more potent than those of BRL37344, isoproterenol and CL-316, 243, respectively. N-5984 had higher selectivity than BRL37344 for human β3-ARs compared with either for β1-ARs or β2-ARs. N-5984 showed higher potency and intrinsic activity of cAMP production than BRL37344 in CHO cells expressing the β3-ARs. CL-316, 243 had almost no activity of cAMP production in CHO cells expressing any subtype of β-ARs. These results indicate that N-5984 is the most potent and selective agonist for human β3-ARs than any other agonists tested.
- Cloned human β-adrenoceptor
- Constitutive activity
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)