Inhibitory effect of neurotensin on gastric acid secretion in rats. Development of a bioassay model.

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.