The metabolism of intravenously infused neurotensin in man and its chromatographic characterization in human plasma.
The metabolism of iv infused neurotensin (NT) was studied and its disappearance half-time compared with that of infused N-terminal octapeptide of NT 1-8 in six normal subjects by RIA with antisera directed against the C- and N-terminal regions of the NT molecule. The disappearance half-time of NT in circulating plasma was 1.4 min measured with the C-terminal antibody and 6.0 min measured with the N-terminal antibody. The disappearance half-time of NT 1-8 was 30 min measured with the N-terminal antibody. Gel filtration and high pressure liquid chromatographic analysis indicated that a substantial amount of immunoreactive NT in the plasma of subjects infused with synthetic NT was eluted at the NT 1-8 position and a lesser amount of plasma NT-like immunoreactivity was eluted with synthetic NT. These findings suggest that NT is readily metabolized in the circulation to NT 1-8. A significant rise in the mean plasma concentration of pancreatic polypeptide was produced by NT, but not by NT 1-8, infused at 2.4 pmol kg-1 min-1. No changes in the mean plasma concentrations of insulin, glucose, or cholesterol were demonstrated during either infusion. The present study suggests that the rapid degradation of NT in man to its N-terminal metabolite may be one of the mechanisms for its bioinactivation in plasma.
D000328:Adult; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D009419:Nerve Tissue Proteins / Q000097:blood; D009479:Neuropeptides; D009496:Neurotensin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D010191:Pancreatic Polypeptide / Q000097:blood; D011863:Radioimmunoassay
D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C031644:neurotensin-like immunoreactivity; D009496:Neurotensin; D010191:Pancreatic Polypeptide