Effect of neurotensin and neurotensin fragments on gastric acid secretion in man

Abstract

The effect of intravenous infusion of neurotensin (NT) and NT-fragments on pentagastrin stimulated gastric acid secretion was investigated in healthy subjects. Neurotensin was infused in three doses (72, 144 and 288 pmol/kg per h). An N-terminal fragment (NT 1–8), a C-terminal fragment (NT 8–13) and an NT-analogue, substituted at the C-terminal tyrosine residue (Phe 11-NT) were infused in two doses (72 and 144 pmol/kg per h). Concentrations of the infused peptides were measured in peripheral venous blood by radioimmunoassay. Plasma levels of NT 1–13, NT 1–8 and Phe 11-NT increased in a dose-dependent manner; NT 1–13 to 50 (34–69), 78 (54–113) and 143 (112–242) pmol/l (medians and range) at 72, 144 and 288 pmol/kg per h, NT 1–8 to 405 (340–465) and 1215 (915–1300) pmol/l, and Phe 11-NT to 200 (110–245) and 390 (250–410) pmol/l at 72 and 144 pmol/kg per h, respectively. Increases in plasma levels of NT 8–13 could not be detected during the infusion, suggesting that the fragment is rapidly metabolized in man. Neurotensin 1–13 inhibited gastric acid secretion in a dose-dependent manner and the decrease in gastric acid secretion was linearly related to plasma levels of NT 1–13. Neurotensin 1–8 and NT 8–13 inhibited gastric acid secretion only at 144 pmol/kg per h, while the analogue Phe 11-NT had no effect. The results showed that the inhibition of gastric acid secretion produced by NT was dose-dependent and linearly related to circulating levels of NT, and that under physiological conditions this effect presumably is elicited by the C-terminal part of the peptide.