The mechanism of the inhibitory action of neurotensin on pentagastrin-stimulated gastric secretion in dogs.

ABSTRACT

Neurotensin is a potent inhibitor of pentagastrin-stimulated gastric acid secretion. This study was done to investigate the possible role of vagal innervation and of prostaglandins on this inhibitory effect. Five dogs with gastric cannulas were infused with pentagastrin (1 microgram per kilogram of body weight each hour) for 210 minutes. In the 60 to 150 minute period, neurotensin (5.5 micrograms per kilogram of body weight each hour) was infused. Neurotensin significantly decreased pentagastrin-stimulated gastric acid output, while the simultaneous administration of indomethacin (bolus of 1 milligram per kilogram of body weight plus infusion of 0.5 milligrams per kilogram each hour) abolished the effect of neurotensin. After truncal vagotomy, the inhibitory effect of neurotensin was again studied. Since the sensitivity of the stomach to pentagastrin decreased after vagotomy, the dose of pentagastrin was doubled (2 micrograms per kilogram of body weight each hour) in order to achieve acid stimulation comparable with the levels before vagotomy. After vagotomy, neurotensin inhibited the effect of pentagastrin in a manner similar to that shown before vagotomy. The inhibitory potency of neurotensin on gastrin-stimulated gastric secretion is independent of the vagus, but requires intact synthesis for prostaglandins.