Atypical β-adrenoceptors mediating relaxation in the human colon:: Functional evidence for β3-rather than β4-adrenoceptors

The aim of the present functional study was to assess the role of beta(3)-adrenoceptors in the light of recent findings suggesting the existence of a putative fourth beta-adrenoceptor in adipose and heart tissue. The effect of the non-conventional beta(3)-adrenoceptor partial agonist CGP12177A is resistant to the effect of the beta(3)-adrenoceptor antagonist SR59230A. Under isotonic conditions in circular muscle strips of human distal colon, the concentration-effect relationship of CGP12177A and SR59104A( beta(3)-adrenoceptor agonists), alone and in the presence of CGP20712A( beta(1)-adrenoceptor antagonist) ICI118551 ( beta(2)-adrenoceptor antagonist) and SR59230A, all 0.1 mu M was studied. CGP12177A concentration-dependently relaxed circular muscle strips (pEC(50) = 6.16 +/- 0.05). This effect was left unchanged by beta(1)-/beta(2)-adrenoceptor blockade, but antagonised by SR59230A (pA(2) = 8.12 +/- 0.02). SR59104A concentration-dependently relaxed circular muscle strips (pEC(50) = 5.43 +/- 0.01), an effect that was not significantly affected by pretreatment with CGP20712A and ICI118551, but competitively antagonised by SR59230A (pK(B) = 7.89). Isoprenaline-induced relaxations were antagonised by propranolol with a low pA(2) value (7.76 +/- 0.16). These results provide further evidence for the presence of functional beta(3)-adrenoceptors in the human colon, but do not support a role for an atypical beta-adrenoceptor distinct from the beta(3)-subtype. (C) 1999 Academic Press.