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.
Hammer
R A
RA
Department of Medicine, Tulane University Medical School, New Orleans, Louisiana 70112.
Hernandez
R E
RE
Shepard
A
A
D000818:Animals; D001681:Biological Assay; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D007262:Infusions, Intravenous / Q000379:methods; D009479:Neuropeptides / Q000097:blood; D009496:Neurotensin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D010418:Pentagastrin / Q000494:pharmacology; D010477:Perfusion / Q000379:methods; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
D009479:Neuropeptides; C031644:neurotensin-like immunoreactivity; D009496:Neurotensin; D010418:Pentagastrin