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Title: Biological potency of neurotensin metabolites in vivo: importance of alcohol 'fixation' of blood.
Austin Authors: Shulkes, Arthur;Fletcher, D R;Hardy, Kenneth John
Affiliation: Department of Surgery, University of Melbourne, Austin Hospital, Victoria, Australia
Issue Date: 10-Sep-1989
Publication information: Journal of Gastroenterology and Hepatology; 4(5): 429-35
Abstract: Neurotensin (NT), a 13-amino acid peptide, is released from the ileum following a meal. It is metabolized principally by the kidney and in the circulation to N-terminal fragments and apparently rapidly degraded C-terminal fragments. The present study was designed to compare the biological activity (plasma pancreatic polypeptide response) and the clearance kinetics of NT(1-13), the N-terminal fragment NT(1-11) and the C-terminal fragment NT(8-13). To measure accurately the circulating concentrations of short-lived NT fragments in the circulation, a method was devised of collecting blood directly into alcohol ('alcohol fixation'). The alcohol fixation procedure prevented the post-collection losses of the C-terminal fragment NT(8-13) and established that, based on blood levels achieved, NT(8-13) had 70% of the pancreatic polypeptide stimulating potency of NT(1-13). Nevertheless, the metabolic clearance rate of NT(8-13) was about sevenfold higher than the intact molecule, NT(1-13), suggesting that circulating C-terminal fragments have a minor physiological role. When the N-terminal fragment NT(1-11) was infused, there was no sustained effect on pancreatic polypeptide secretion although it was cleared at a rate similar to that of NT(1-13). It is concluded that the use of alcohol fixation prevents post-collection losses of NT fragments and enables true biological potencies of short-lived fragments to be assessed. The biological activity of NT resides in the C-terminus which, once split from the protective N-terminus, is rapidly degraded in the circulation. The remaining intact but inactive N-terminus is relatively stable.
Gov't Doc #: 2491208
Type: Journal Article
Subjects: Animals
Blood Specimen Collection.methods
Metabolic Clearance Rate
Pancreatic Polypeptide.metabolism
Peptide Fragments.metabolism
Appears in Collections:Journal articles

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