beta(3)-Adrenoceptors mediating relaxation of the oesophageal 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 relaxations was similar in the two tissues. 3 BRL 37344 was a partial agonist relative to isoprenaline in the colon but when a single maximal concentration of BRL 37344 (1 mu M) was added, a full relaxation was observed. 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 37344. 6 The present study demonstrates that the beta-adrenoceptors mediating relaxation in both the rat isolated distal colon and oesophagus are of the beta(3)-adrenoceptor subtype. Desensitization appears to result from the binding of BRL 37344 to the beta(3)-adrenoceptor in a manner which is blockable by cyanopindolol.