The stability and metabolism of intravenously administered neurotensin in the rat

Peptides. Jul-Aug 1982;3(4):637-42. doi: 10.1016/0196-9781(82)90164-4.

Abstract

The clearance and metabolism of synthetic and tritiated (3H) neurotensin (NT) were studied following its intravenous injection in a pharmacologic dose (500 pmol/kg) into anesthesized rats. Immunoreactive NT (iNT), measured in a radioimmunoassay (RIA) with use of a carboxyl-(C)-terminal directed antiserum, displayed an apparent half-life (t 1/2) of 0.55 min, while that measured by an amino-(N)-terminal directed antiserum had a t 1/2 of 5 min. The radiolabel from injected 3H-NT (3H on Tyr3,11) had a t 1/2 of 6.5 min. High-pressure liquid chromatography of extracts of plasma obtained from the circulation 0.5-3 min after injection of NT and 3H-NT showed the presence of NT and the generation mainly of the fragments NT1-8, NT1-11, and NT9-13, as well as free 3H-labeled tyrosine. The apparent half-lives of intravenously injected synthetic NT1-8, NT1-11 and NT1-12 measured with the N-terminal RIA were 9, 5 and 5 min, respectively, while that for NT9-13 was less than 0.5 min. These results indicate that exogenously injected NT is rapidly metabolized to form N-terminal fragments which are cleared more slowly than NT. These findings suggest that use of N-terminal antisera to detect the release of endogenous NT into the circulation is likely to yield measurements of the fragments NT1-8 and NT1-11 which thus far have been found to be biologically inactive.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chromatography, Gel
  • Chromatography, High Pressure Liquid
  • Female
  • Half-Life
  • Injections, Intravenous
  • Male
  • Neurotensin / blood*
  • Peptide Fragments / blood
  • Radioimmunoassay
  • Rats

Substances

  • Peptide Fragments
  • Neurotensin