Pharmacological evidence for [beta]^sub 3^ adrenoceptors in the control of rat gastric acid secretion

The effect of the beta3-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 beta2-adrenoceptor agonist clenbuterol. Intravenous injections of BRL37344 (1-10 micromol/kg) and clenbuterol (0.01-1 micromol/kg) dose-dependently reduced 2-deoxy-D-glucose-induced acid secretion, with BRL37344 about forty times less potent than clenbuterol. BRL37344 (0.1-3 micromol/kg) inhibited pentagastrin-induced acid output, whereas clenbuterol was effective only at high doses (10-100 micromol/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 beta3-adrenoceptor antagonist. Furthermore, neither BRL37344 (10 micromol/kg) nor clenbuterol (100 micromol/kg) modified the acid secretion induced by histamine. These data suggest that beta3 adrenoceptors have an inhibitory role in the control of rat gastric acid secretion induced by indirect stimuli.