BETA(3)-ADRENOCEPTORS MEDIATING RELAXATION OF THE ESOPHAGEAL TUNICA MUSCULARIS MUCOSAE AND DISTAL COLON IN THE RAT - COMPARATIVE PHARMACOLOGY AND THEIR DESENSITIZATION BY BRL-37344

1 In the rat isolated distal colon and oesophagus, relaxant responses to (-)-isoprenaline were poorly antagonized by propranolol (0.1 mu M), suggesting an involvement of beta(3)-adrenoceptors. 2 In the presence of propranolol the rank order of potency for the agonist-induced rela xations was similar in the two tissues. 3 BRL 37344 was a partial agon ist relative to isoprenaline in the colon but when a single maximal co ncentration of BRL 37344 (1 mu M) was added, a full relaxation was obs erved. 4 BRL 37344 desensitized responses to isoprenaline in both the colon and oesophagus. 5 (+/-)-Cyanopindolol (1.0 mu M) antagonized the relaxatory responses to both isoprenaline and BRL 37344 in the distal colon and oesophagus and reduced the desensitizing effect of BRL 3734 4. 6 The present study demonstrates that the beta-adrenoceptors mediat ing relaxation in both the rat isolated distal colon and oesophagus ar e of the beta(3)-adrenoceptor subtype. Desensitization appears to resu lt from the binding of BRL 37344 to the beta(3)-adrenoceptor in a mann er which is blockable by cyanopindolol.