Atypical beta-adrenoceptors mediating relaxation in the human colon: functional evidence for beta3-rather than beta4-adrenoceptors.
The aim of the present functional study was to assess the role of beta3-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 beta3-adrenoceptor partial agonist CGP12177A is resistant to the effect of the beta3-adrenoceptor antagonist SR59230A. Under isotonic conditions in circular muscle strips of human distal colon, the concentration-effect relationship of CGP12177A and SR59104A (beta3-adrenoceptor agonists), alone and in the presence of CGP20712A (beta1-adrenoceptor antagonist) ICI118551 (beta2-adrenoceptor antagonist) and SR59230A, all 0.1 microm was studied. CGP12177A concentration-dependently relaxed circular muscle strips (pEC50=6.16+/-0.05). This effect was left unchanged by beta1-/beta2-adrenoceptor blockade, but antagonised by SR59230A (pA2=8.12+/-0.02). SR59104A concentration-dependently relaxed circular muscle strips (pEC50=5.43+/-0.01), an effect that was not significantly affected by pretreatment with CGP20712A and ICI118551, but competitively antagonised by SR59230A (p KB=7.89). Isoprenaline-induced relaxations were antagonised by propranolol with a low pA2value (7.76+/-0.16). These results provide further evidence for the presence of functional beta3-adrenoceptors in the human colon, but do not support a role for an atypical beta-adrenoceptor distinct from the beta3-subtype.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003106:Colon / Q000187:drug effects*; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D022702:Receptors, Adrenergic, beta-3; D013764:Tetrahydronaphthalenes / Q000494:pharmacology