The β3-adrenoceptor agonist SR58611A inhibits gastric acid secretion in the conscious cat

Abstract

The effect of the β₃-adrenoceptor agonist {N-[(2S)-7-ethoxycarbonyl-methoxyl-1, 2, 3, 4-tetrahydro-naphth-2-yl] (2R)-2-(3-chloro-phenyl)2-hydroxyethanamine hydrochloride} (SR58611A) on gastric acid secretion was investigated in conscious cats with a gastric fistula. Intravenous infusion of SR58611A (0.3–3μmol/kg/h) caused a dose-dependent inhibition of the acid secretion stimulated by 2-deoxy-D-glucose (2DG), with a maximum reduction by 45%. The secretory effect of the histamine H₂-receptor agonist dimaprit only tended to be reduced by SR58611A (3μmol/kg/h). The inhibitory effect of SR58611A was not modified by the non selective β₁- and β₂-adrenoceptor antagonist propranolol (1.5μmol/kg i.v.), but it was prevented by bupranolol (10μmol/kg i.v.), a drug endowed with β₃-antagonistic properties. Both antagonists blocked the inhibitory effect of the β₂-adrenoceptor agonist clenbuterol (0.1μmol/kg/h) on 2DG-induced acid secretion. These findings suggest that compound SR58611A inhibits gastric acid secretion in the conscious cat through activation of β₃-adrenoceptors insensitive to propranolol.