The beta3-adrenoceptor agonist SR58611A inhibits gastric acid secretion in the conscious cat.
The effect of the beta3-adrenoceptor agonist [ N-[(2S)-7-ethoxycarbonyl-methoxyl-1,2,3,4-tetrahydronaphth-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 (0.3-3 micromol/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 (3 micromol/kg/h). The inhibitory effect of SR5861 IA was not modified by the non selective beta1- and beta2-adrenoceptor antagonist propranolol (1.5 micromol/kg i.v.), but it was prevented by bupranolol (10 micromol/kg i.v.), a drug endowed with beta3-antagonistic properties. Both antagonists blocked the inhibitory effect of the beta2-adrenoceptor agonist clenbuterol (0.1 micromol/kg/h) on 2DG-induced acid secretion. These findings suggest that compound SR58611A inhibits gastric acid secretion in the conscious cat through activation of beta3-adrenoceptors insensitive to propranolol.
Coruzzi
G
G
Institute of Pharmacology, University of Parma, Italy.
Bertaccini
G
G
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D002976:Clenbuterol / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D013764:Tetrahydronaphthalenes; C076252:amibegron; D002976:Clenbuterol