Effects of diazepam and Ro 15-1788 on duodenal bicarbonate secretion in the rat.

Bicarbonate secretion by duodenal mucosa just distal to the Brunner's glands area and devoid of pancreatic secretions was titrated in situ in anesthetized rats. Intravenous injection of diazepam (0.1 and 0.5 mg/kg) significantly increased the secretion; this stimulation was abolished by proximal bilateral vagotomy. Ro 15-1788, a benzodiazepine antagonist that also has well-known intrinsic activity, caused similar stimulation of the secretion when administered IV (0.01 and 0.1 mg/kg). Intracerebroventricular infusion of Ro 15-1788 (10 micrograms/h) resulted in a greater increase in secretion; again, this stimulation was prevented by vagotomy. Adrenoceptor blockade by phentolamine increased basal alkaline secretion but did not affect the stimulation by diazepam. The tricyclic antidepressant trimipramine (2.5 mg/kg IV) did not affect the duodenal bicarbonate secretion. For comparison, effects of diazepam and Ro 15-1788 (10(-6)-10(-4) mol/L) were also tested in isolated bullfrog duodenal mucosa. Neither drug effected the alkaline secretion in vitro. The combined results strongly suggest that benzodiazepines, as previously shown for certain brain peptides, influence the central nervous control of duodenal mucosal alkaline secretion and that their stimulation of secretion is vagally mediated. This action benzodiazepines might be used in modulating mucosal protection against acid.