THE BETA-ADRENOCEPTORS MEDIATING RELAXATION OF RAT ESOPHAGEAL MUSCULARIS MUCOSAE ARE PREDOMINANTLY OF THE BETA(3)-, BUT ALSO OF THE BETA(2)-SUBTYPE

1 Beta-Adrenoceptor-mediated relaxation of rat oesophageal smooth musc le was investigated by studying the effects of beta1- and beta2-select ive antagonists on the relaxation induced by (-)-isoprenaline, the bet a2-selective agonists fenoterol and clenbuterol and the beta3-agonist, BRL 37344. 2 The highly beta1-selective antagonist CGP 20712A did not antagonize (-)-isoprenaline- or BRL 37344-induced relaxations in conc entrations up to 10 muM. Only at 100 mum of CGP 20712A were clear righ tward shifts of the agonist concentration-response curves (CRCs) obser ved, with pA2 values of 4.70 and 4.97 against (-)-isoprenaline and BRL 37344, respectively. 3 ICI 118,551, a potent and selective beta2-anta gonist, at 100 nm caused moderate rightward shifts of the CRCs of (-)- isoprenaline, fenoterol and clenbuterol; with fenoterol and clenbutero l, this was accompanied by a clear steepening of the curve. Only at th e highest concentration (100 mum ICI 118,551) did the shifts to the ri ght further increase substantially. Resulting Schild-plots were clearl y biphasic. BRL 37344-induced relaxations were only antagonized at 100 mum ICI 118,551, yielding a pA2 value of 5.48. 4 These results clearl y demonstrate that the BRL 37344-induced relaxation of rat oesophageal muscularis mucosae is mediated solely through beta3-adrenoceptors, wh ereas (-)-isoprenaline-, fenoterol- and clenbuterol-induced relaxation s were shown to involve both beta2- and, predominantly, beta3-adrenoce ptors.