Inhibitory effect of neurotensin on gastric acid secretion in rats

Abstract

Neurotensin has been shown to inhibit gastric acid secretion when administered in pharmacological doses, but no information has been available concerning its possible dose-related effect during intravenous infusion. In this study, a dose-related and reversible inhibitory effect of neurotensin was demonstrated in pentobarbital-anesthetized female Sprague-Dawley rats. The rats underwent continuous gastric perfusion with saline, 1 ml/min, and intravenous infusion of both pentagastrin and neurotensin. Inhibition of acid secretion did not depend upon the occurrence of hypotension, and ranged from 35 +/- 7% of maximal acid output at 0.24 nmol/kg/hr to 60 +/- 10% at 7.2 nmol/kg/hr of neurotensin. Blood levels of C-terminal neurotensin-like immunoreactivity were proportional to the dose of peptide infused and were 52 fmol/ml during infusion of 0.24 nmol/kg/hr, a dose that significantly inhibited pentagastrin-induced acid secretion. Thus, a model has been developed to study the effect of neurotensin infusion on acid secretion; the concentration of plasma neurotensin-like immunoreactivity at which inhibition occurs in this model is similar to the concentration reported to occur after a nutrient stimulus.