FUNCTIONAL EVIDENCE FOR THE PRESENCE OF BETA(3)-ADRENOCEPTORS IN THE GUINEA-PIG COMMON BILE-DUCT AND COLON

To determine the existence of beta(3)-adrenoceptors in functional assa ys in isolated preparations for which data are lacking, we compared th e effects of SR 58611A, a selective beta(3)-adrenoceptor agonist, and isoprenaline in the guinea pig common bile duct, distal colon and urin ary bladder. SR 58611A and isoprenaline relaxed the common bile duct ( EC(50): 6.85 and 0.41 mu mol/l, respectively). The effect of SR 58611A was resistant to CGP 20712A, ICI 118551, propranolol and tetrodetoxin , but was antagonized by alprenolol (pA(2) = 6.86), while the effect o f isoprenaline was antagonized by CGP 20712A, ICI 118551, propranolol and alprenolol (pA(2) = 7.04, in the presence of propranolol to satura te beta(1)- and beta(2)-adrenoceptors). In colonic preparations, SR 58 611A and isoprenaline relaxed circular muscle strips (EC(50): 5.48 and 0.49 mu mol/l, respectively). The effect of SR 58611A was resistant t o CGP 20712A, ICI 118551, propranolol and tetrodotoxin, but was antago nized by alprenolol (pA(2) = 7.01). The effect of isoprenaline was res istant to CGP 20712A, but was antagonized by ICI 118551, propranolol a nd alprenolol (pA(2) = 6.88, in the presence of propranolol). In urina ry bladder strips, SR 58611A had no effect, whereas isoprenaline reduc ed resting tone (EC(50): 0 87 mu mol/l), an effect antagonized by alpr enolol (pA(2) = 8.14). These data provide functional evidence for the presence of beta(3)-adrenoceptors in the guinea pig common bile duct a nd colon, but not in the urinary bladder. At the concentrations used, the effect of SR 58611A was probably mediated solely by activation of beta(3)-adrenoceptors located on smooth muscle cells, whereas the effe cts of isoprenaline were due to beta(3)- and also to beta(1)- and/or b eta(2)-adrenoceptor activation.