Effects of beta3-adrenoceptor agonist SR 58611A on gastric acid secretion and histamine release in the dog: comparison with ritodrine.

1. The involvement of beta3 adrenoceptors in the control of gastric acid secretion and histamine release was investigated in the dog. 2. In conscious dogs, SR 58611A (0.0625-1.0 mg/kg/hr i.v.) dose dependently inhibited gastric acid secretion induced by pentagastrin. Maximal inhibition (40%) was obtained with the dose of 1 mg/kg. Ritodrine (1 mg/kg/hr i.v.) also induced a marked inhibition (85%) of gastric acid secretion stimulated by pentagastrin. 3. On 2-deoxy-D-glucose-stimulated acid secretion, both SR 58611A and ritodrine at 1 mg/kg/hr i.v. showed inhibitory effects. On these experiments, ritodrine, but not SR 58611A, significantly reduced plasma gastrin concentrations. 4. In anaesthetized dogs, histamine concentrations from gastrosplenic vein increased fivefold after the infusion of pentagastrin. SR 58611A (1 mg/kg/hr i.v.) did not significantly modify the stimulant effect of pentagastrin on histamine release. In contrast, ritodrine (1 mg/kg/hr i.v.) significantly inhibited histamine release induced by pentagastrin. 5. These data suggest that beta3 adrenoceptors may participate in the negative control of gastric acid secretion in the dog, probably through a histamine-independent mechanism.