Man and Its Chromatographic Characterization in Human Plasma

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Abstract
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 Nterminal regions of the NT molecule. The disappearan x halftime of NT in circulating plasma was 1.4 min measured with the C-terminal antibody and 6.0 min measured with the N-teiminal antibody. The disappearance half-time of NT 1-8 was 31 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.