Agonistic activity of SR59230A at atypical β-adrenoceptors in guinea pig gastric fundus and duodenum

We have recently suggested that atypical P-adrenoceptors are present in guinea pig gastric fundus and duodenum. In the present study, we have shown that SR59230A (3-(2-ethylphenoxy)-1-[(1S)-1,2,3,4-tetrahydronaphth-1-ylamino]-(2S)-2-propanol oxalate), a selective beta (3)-adrenoceptor antagonist, possesses agonistic activities at atypical beta -adrenoceptors in these tissues. SR59230A caused concentration-dependent relaxations. However, (+/-)-propranolol(1 muM) did not affect SR59230A-induced relaxations. Pretreatment of with a combination of (+/-)-propranolol (1 muM) and the non-selective beta (1)-, beta (2)-, beta (3)- and beta (4)-adrenoceptor antagonist, (+/-)-bupranolol (30 muM), significantly antagonized the relaxant effects induced by SR59230A. The results clearly indicate that SR59230A acts as an atypical beta -adrenoceptor agonist on guinea pig gastric fundus and duodenum. (C) 2001 Elsevier Science B.V. All rights reserved.