BETA(3)-ADRENOCEPTORS MEDIATE SMOOTH-MUSCLE RELAXATION IN THE RAT LOWER ESOPHAGEAL 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) re laxed ring segments of the LOS in a concentration-dependent manner. Pr opranolol (10(-7) M) had very little antagonist effect on isoprenaline -induced relaxation. 3 Dobutamine (10(-7) M - 10(-4) M), salbutamol (1 0(-7) M - 10(-4) M) and BRL 37344 (10(-8) - 10(-5) M) also all relaxed carbachol-contracted ring segments of the LOS in a concentration-depe ndent 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, dobutamin e, 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 T he relaxant effect of isoprenaline in the rat LOS was not inhibited by N-G-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)-adreno ceptors mediate isoprenaline-induced relaxation in rat lower oesophage al sphincter and that activation of these receptors was not linked to either ATPase-, Ca2+-dependent K+ channels or to NO release.