Beta(3)-adrenoceptors mediate smooth muscle relaxation in the rat lower oesophageal sphincter

1. The role of beta(3)-adrenoceptors in isoprenaline-induced relaxation of carbachol-precontracted ring segments of the rat lower oesophageal sphincter (LOS) was examined. 2. Isoprenaline (10(-8)M-10(-5)M) relaxed ring segments of the LOS in a concentration-dependent manner. Propranolol (10(-7)M) had very little antagonist effect on isoprenaline-induced relaxation. 3. Dobutamine (10(-7)M-10(-4)M), salbutamol (10(-7)-10(-4)M) and BRL 37344 (10(-8)-10(-5)M) also relaxed carbachol-contracted ring segments of the LOS in a concentration-dependent manner. The relaxant responses to these agonists were similarly not antagonized by propranolol (10(-7)M). 4. Cyanopindolol (10(-6)M), produced a parallel rightward displacement of isoprenaline, dobutamine, salbutamol and BRL 37344 concentration-response curves with similar potencies. The pKB values range from 7.3 +/- 0.1 to 7.7 +/- 0.2. 5. The relaxant effect of isoprenaline in the rat LOS was not inhibited by NG-nitro-L-arginine (L-NOARG; 3 x 10(-5)M), glibenclamide (10(-5)M) or tetraethylammonium (1 mM). 6. It was concluded that beta(3)-adrenoceptors mediate isoprenaline-induced relaxation in rat lower oesophageal sphincter and that activation of these receptors was not linked to either ATPase-, Ca(2+)-dependent K+ channels or to NO release.