Pharmacological evidence for beta3 adrenoceptors in the control of rat gastric acid secretion

The effect of the beta(3)-adrenoceptor agonist BRL37344 on gastric acid secretion evoked by different secretory stimuli was investigated in anaesthetized rats with lumen-perfused stomachs in comparison with the beta(2)-adrenoceptor agonist clenbuterol. Intravenous injections of BRL37344 (1-10 mumol/kg) and clenbuterol (0.01-1 mumol/kg) dose-dependently reduced 2-deoxy-D-glucose-induced acid secretion, with BRL37344 about forty times less potent than clenbuterol. BRL37344 (0.1-3 mumol/kg) inhibited pentagastrin-induced acid output, whereas clenbuterol was effective only at high doses (10-100 mumol/kg). The inhibitory effect of BRL37344 on pentagastrin-induced acid secretion was not modified by the nonselective beta-adrenoceptor antagonist propranolol, but it was prevented by bupranolol, a beta(3)-adrenoceptor antagonist. Furthermore, neither BRL37344 (10 mumol/kg) nor clenbuterol (100 mumol/kg) modified the acid secretion induced by histamine. These data suggest that beta(3) adrenoceptors have an inhibitory role in the control of rat gastric acid secretion induced by indirect stimuli