β3-Adrenoceptors mediate smooth muscle relaxation in the rat lower oesophageal sphincter

1 The role of β₃-adrenoceptors in isoprenaline-induced relaxation of carbachol-precontracted ring segments of the rat lower oesophageal sphincter (LOS) was examined. 2 Isoprenaline (10^?8m – 10^?5m ) relaxed ring segments of the LOS in a concentration-dependent manner. Propranolol (10^?7m ) had very little antagonist effect on isoprenaline-induced relaxation. 3 Dobutamine (10^?7m – 10^?4m ), salbutamol (10^?7m – 10^?4m ) and BRL 37344 (10^?8– 10^?5m ) also all 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^?7m ). 4 Cyanopindolol (10^?6m ), produced a parallel rightward displacement of isoprenaline, dobutamine, salbutamol and BRL 37344 concentration–response curves with similar potencies. The pK_B 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 N^G-nitro-l -arginine (l -NOARG; 3 × 10^?5m ), glibenclamide (10^?5m ) or tetraethylammonium (1 mm ). 6 It was concluded that β₃-adrenoceptors mediate isoprenaline-induced relaxation in rat lower oesophageal sphincter and that activation of these receptors was not linked to either ATPase-, Ca²⁺-dependent K⁺ channels or to NO release.