EFFECTS OF BETA(3)-ADRENOCEPTOR AGONIST SR 58611A ON GASTRIC-ACID SECRETION AND HISTAMINE-RELEASE IN THE DOG - COMPARISON WITH RITODRINE

1. The involvement of beta(3) adrenoceptors in the control of gastric acid secretion and histamine release was investigated in the dog. 2. I n conscious dogs, SR 58611A (0.0625-1.0 mg/kg/hr IV) dose dependently inhibited gastric acid secretion induced by pentagastrin. Maximal inhi bition (40%) was obtained with the dose of 1 mg/kg. Ritodrine (1 mg/kg /hr IV) also induced a marked inhibition (85%) of gastric acid secreti on stimulated by pentagastrin. 3. On 2 deoxy-D-glucose-stimulated acid secretion, both SR 58611A and ritodrine at 1 mg/kg/hr IV showed inhib itory effects. On these experiments, ritodrine, but not SR 58611A, sig nificantly reduced plasma gastrin concentrations. 4. In anaesthetized dogs, histamine concentrations from gastrosplenic vein increased fivef old after the infusion of pentagastrin. SR 58611A(1 mg/kg/hr IV) did n ot significantly modify the stimulant effect of pentagastrin on histam ine release. Tn contrast, ritodrine (1 mg/kg/hr IV) significantly inhi bited histamine release induced by pentagastrin. 5. These data suggest that beta(3) adrenoceptors may participate in the negative control of gastric acid secretion in the dog, probably through a histamine-indep endent mechanism. (C) 1998 Elsevier Science Inc.