Functional evidence of atypical β3-adrenoceptors in the human colon using the β3-selective adrenoceptor antagonist, SR 59230A

Abstract

The role of β3-adrenoceptors in human colonic circular smooth muscle was assessed in vitro by use of the β3-selective antagonist SR 59230A. Isoprenaline, in the presence of the selective β-adrenoceptor antagonists CGP 20712A (β1) and ICI 118551 (β2), both at 0.1 μM, concentration-dependently relaxed the preparation (pEC50=5.22). This effect was potently and competitively antagonized by SR 59230A with a pA, of 8.31, while its R,R enantiomer SR 59483A gave an apparent pK(B) of 6.21. Relaxation was likewise produced by CGP 12177A (PEC50 = 6.05), but not by BRL 37344. Although only one of these β3-selective agonists was effective, the remarkably high potency of SR 59230A as a stereospecific antagonist of non-β1 non-β2 relaxation of human colonic muscle by isoprenaline provides strong functional evidence of β3-adrenoceptors in that tissue.