FUNCTIONAL EVIDENCE OF ATYPICAL BETA(3)-ADRENOCEPTORS IN THE HUMAN COLON USING THE BETA(3)-SELECTIVE ADRENOCEPTOR ANTAGONIST, SR 59230A

The role of beta(3)-adrenoceptors in human colonic circular smooth mus cle was assessed in vitro by use of the beta(3)-selective antagonist S R 59230A. Isoprenaline, in the presence of the selective P-adrenocepto r antagonists CGP 20712A (beta(1)) and ICI 118551 (beta(2)), both at 0 .1 mu M, concentration-dependently relaxed the preparation (pEC(50) = 5.22). This effect was potently and competitively antagonized by SR 59 230A with a pA(2) 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 (pEC(50)=6.05), but not by BRL 37344. Although only one of these beta (3)-selective agonists was effective, the remarkably high potency of S R 59230A as a stereospecific antagonist of non-beta(1) non-beta(2) rel axation of human colonic muscle by isoprenaline provides strong functi onal evidence of beta(3)-adrenoceptors in that tissue.