AJP - Endocrinology and Metabolism, Vol 245, Issue 5 457-E462, Copyright © 1983 by American Physiological Society
Organ and plasma metabolism of neurotensin in sheep
A. Shulkes, D. R. Fletcher and K. J. Hardy
The metabolism of neurotensin (NT) across specific vascular beds of
conscious sheep and the stability of NT in plasma have been quantitated.
The nature of the metabolites has been characterized with region-specific
antiserums and chromatography. NT-(1-13) was infused at 200 pmol X kg-1 X
h-1 for 60 min into nine ewes, and blood samples were taken via cannulas in
the aorta, pulmonary artery, portal vein, hepatic vein, renal vein, and
jugular vein. Two antiserums, one directed towards the N-terminal end of NT
(7852) and the other directed to the C-terminal end (C28) were used for
radioimmunoassay. Pancreatic polypeptide (PP) was measured also. Using the
steady-state concentrations in the aorta, the metabolic clearance rate of
NT measured with C28 was 25.8 +/- 3.2 ml X kg-1 X min-1, twice that with
7852. The kidney, brain, and gut were the major organs clearing NT with a
greater disappearance of C-terminal than N-terminal immunoreactivity. Gel
chromatography of plasma at steady state showed that the NT
immunoreactivity consisted of intact NT and N-terminal fragments; no
C-terminal fragments were detected. Similarly, incubation of NT in plasma
in vitro resulted in the generation of stable N-terminal fragments. The
kidney was also the major organ involved in the clearance of PP both in the
basal state and after stimulation by NT. Because the C-terminal end of NT
is biologically active, these studies suggest that either N-terminal
fragments have some unknown biological role or that NT is acting as a local
hormone.
