De Ponti F, Gibelli G, Croci T, Arcidiaco M, Crema F, Manara L
Department of Internal Medicine and Therapeutics, University of Pavia, Italy.
Br J Pharmacol. 1996 Apr;117(7):1374-6. doi: 10.1111/j.1476-5381.1996.tb15294.x.
The role of beta 3-adrenoceptors in human colonic circular smooth muscle was assessed in vitro by use of the beta 3-selective antagonist SR 59230A. Isoprenaline, in the presence of the selective beta-adrenoceptor antagonists CGP 20712A (beta 1) and ICI 118551 (beta 2), both at 0.1 microM, concentration-dependently relaxed the preparation (pEC50 = 5.22). This effect was potently and competitively antagonized by SR 59230A with a pA2 of 8.31, while its R,R enantiomer SR 59483A gave an apparent pKB of 6.21. Relaxation was likewise produced by CGP 12177A (pEC50 = 6.05), but not by BRL 37344. Although only one of these beta 3-selective agonists was effective, the remarkably high potency of SR 59230A as a stereospecific antagonist of non-beta 1 non-beta 2 relaxation of human colonic muscle by isoprenaline provides strong functional evidence of beta 3-adrenoceptors in that tissue.
利用β3选择性拮抗剂SR 59230A在体外评估了β3肾上腺素能受体在人结肠环行平滑肌中的作用。在选择性β肾上腺素能受体拮抗剂CGP 20712A（β1）和ICI 118551（β2）均为0.1微摩尔的情况下，异丙肾上腺素使标本呈浓度依赖性舒张（pEC50 = 5.22）。SR 59230A对该效应有强效竞争性拮抗作用，pA2为8.31，而其R,R对映体SR 59483A的表观pKB为6.21。CGP 12177A同样可产生舒张作用（pEC50 = 6.05），但BRL 37344则不能。尽管这些β3选择性激动剂中只有一种有效，但SR 59230A作为异丙肾上腺素对人结肠肌肉非β1非β2舒张的立体特异性拮抗剂具有极高的效力，这为该组织中存在β3肾上腺素能受体提供了有力的功能证据。
