Comparison between β3 and β2 adrenoceptor agonists as inhibitors of gastric acid secretion

In order to investigate the role of beta(3) adrenoceptors in the regulation of gastric acid secretion we studied the effects of compound SR58611A (a selective agonist for atypical beta adrenoceptors), alone or in combination with beta-adrenoceptor antagonists, in the gastric fistula of a conscious cat. The effects of SR58611A were compared with those of clenbuterol, a selective agonist for beta(2) adrenoceptors. Intravenous infusion of SR58611A (0.3-3 mu mol/kg/h) caused a dose-dependent, but partial, inhibition of the acid secretory response to 2-deoxy-D-glucose 100 mg/kg iv, maximum effect not exceeding 40%. Clenbuterol (0.03-0.1 mu mol/kg/h) caused a similar effect (maximum inhibition about 50%) at doses approximately 30 times lower. The acid secretion induced by the histamine H-2-receptor agonist dimaprit (1 mu mol/kg/h) was minimally affected by both beta adrenoceptor agonists. The inhibitory effect of SR58611A (3 mu mol/kg/h) on 2-deoxy-D-glucose-induced acid secretion was not modified by pretreatment with the non-selective beta(1)-and beta(2)-adrenoceptor blocker propranolol, administered at doses (1.5 mu mol/g iv) that completely blocked the inhibitory effect of clenbuterol (0.1 mu mol/kg/h). In contrast, bupranolol (10 mu mol/kg iv) (a drug endowed with beta(3) antagonistic properties) prevented the inhibitory effects of both SR58611A and clenbuterol. The present data provide functional evidence that, besides beta(2)-, also beta(3)-adrenoceptors can have negative effects on gastric acid secretion, particularly when it is stimulated by indirect stimuli, like 2-deoxy-D-glucose. This gastric antisecretory activity may represent an additional mechanism for the physio-pharmacological control of gastric acid secretion.