Functional properties of atypical β-adrenoceptors on the guinea pig duodenum

In this study, we attempted to further characterize atypical beta -adrenoceptors on the guinea pig duodenum. (-)-Enantiomers of isoprenaline and noradrenaline were more potent than its(+)-enantiomers. The isomeric activity ratios ((+)/(-)) were less than those obtained in the guinea pig atria and trachea. The concentration-response curves to catecholamines ((-)-isoprenaline, (-)-noradrenaline and (-)-adrenaline), to the selective beta (3)-adrenoceptor agonist, BRL37344 ((R*, R*)-(+/-)-4-[2-[(2-(3-chlorophenyl)-2-hydroxy-ethyl)amino]propyl]phenoxyacetic acid sodium), and to the non-conventional partial beta (3)-adrenoceptor agonist, (+/-)-CGP12177A ((+/-)-[4-[3-[(1,1 -dimethylethyl)-amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one] hydrochloride), were resistant to blockade by (+/-)-pindobind, the beta -adrenoceptor alkylating agent. (-)-Noradrenaline and(-)-adrenaline were more potent than dopamine and (-)-phenylephrine, respectively. Selective beta (2)-ladrenoceptor agonists possess agonistic activities at atypical beta -adrenoceptors. (+/-)-Propranolol and (+/-)-bupranolol had no agonistic effect, whereas (+/-)-alprenolol, (+/-)-pindolol, (+/-)-nadolol, (+/-)-CGP12177A and (+/-)-carteolol exhibited agonistic activities at atypical beta -adrenoceptors. These results suggest that pharmacological properties of atypical beta -adrenoceptors differ from those of conventional beta (1)- and beta (2)-adrenoceptors on the guinea pig. (C) 2001 Published by Elsevier Science B.V.