Selectivity and potency of agonists for the three subtypes of cloned human β-adrenoceptors expressed in Chinese hamster ovary cells

Teruyuki Yanagisawa, Takeya Sato, Hiroaki Yamada, Jun Sukegawa, Kazuo Nunoki

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)181-193
Number of pages13
JournalTohoku Journal of Experimental Medicine
Volume192
Issue number3
DOIs
Publication statusPublished - 2000 Nov

Keywords

  • BRL37344
  • Cloned human β-adrenoceptor
  • Constitutive activity
  • Isoproterenol
  • N-5984

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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