Characterisation of the atypical beta-adrenoceptor in rabbit isolated jejunum using BRL 37344, cyanopindolol and SR 59230A

1 The present study was carried out to further investigate the nature of th e p-adrenoceptor in rabbit jejunum using BRL 37344, a selective beta(3)-adr enoceptor agonist, cyanopindolol, a beta-adrenoceptor antagonist with block ing activity at beta(3)-adrenoceptors and SR 59230A, a new selective beta(3 )-adrenoceptor antagonist. 2 Isoprenaline produced a concentration-dependent inhibition of the spontan eous contractions of rabbit jejunum with a pot of 7.14. Propranolol (1 mu M ) shifted the isoprenaline concentration-response curve (CRC) to the right with a concentration-ratio of 5.85, considerably less than would be expecte d for an action at classical p-adrenoceptors (estimated pA(2) 6.66). 3 BRL 37344 also produced a concentration-dependent inhibition of spontaneo us contractions with a pD(2) of 7.41. The BRL 37344 CRC was unaffected by p ropranolol (1 mu M). 4 In the presence of propranolol (1 mu M), cyanopindolol (1 mu M) shifted t he isoprenaline CRC to the right (concentration-ratio of 21). Cyanopindolol also shifted the BRL 37344 CRC to the right (concentration-ratio of 38). T hese shifts are consistent with the affinity of cyanopindolol for beta(3)- adrenoceptors (estimated pA2 values of 7.27 and 7.38 against isoprenaline a nd BRL 37344, respectively). 5 In the presence of propranolol (1 mu M), SR 59230A produced a concentrati on-dependent rightward shift of the isoprenaline CRC. The Schild plot gave a pA(2) value of 7.16, although the slope of the regression line was signif icantly different from unity (0.65). SR 59230A also produced a concentratio n-dependent shift of the BRL 37344 CRC. The Schild plot gave a pA(2) of 7.5 8 with the slope of the regression line not significantly different from un ity (0.81). 6 The presence of beta(3)-adrenoceptors mediating relaxation of spontaneous contractions in rabbit jejunum is supported by the relatively poor antagon ism of isoprenaline by propranolol, the relaxant effect of BRL 37344 and th e antagonism of isoprenaline and BRL 37344 by cyanopindolol and SR 59230A. The lack of simple competitive antagonism of isoprenaline, but not BRL 3734 4, by SR 59230A may suggest more than one population of atypical beta-adren oceptor.