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Title: Pharmacokinetics and biological activity of kinetensin in conscious sheep.
Austin Authors: Read, D M;Shulkes, Arthur;Fletcher, D;Hardy, Kenneth John
Affiliation: Department of Surgery, University of Melbourne, Austin Hospital, Victoria, Australia
Issue Date: 1-Mar-1993
Publication information: Agents and Actions; 38(3-4): 231-9
Abstract: Kinetensin is a nonapeptide, originally isolated from pepsin-treated plasma, that shares some sequence homology with the C-terminal end of neurotensin. The present study was designed to determine, by infusing kinetensin to conscious sheep, the pharmacokinetics and a neurotensin-like biological activity (pancreatic polypeptide response) of kinetensin. Kinetensin was rapidly metabolized, approximately 200-fold more rapidly than neurotensin. The majority of the metabolism occurred in the circulation as demonstrated both in vivo and in vitro. The lung and gut cleared kinetensin also. Inhibition of converting enzyme, present in highest concentration in the lung, abolished lung clearance but was without effect on kinetensin metabolism by the gut or in the general circulation. Arterial infusion of kinetensin which achieved high blood kinetensin levels at the pancreas did not increase plasma pancreatic polypeptide. We conclude that the extremely rapid degradation of exogenous kinetensin, together with the lack of biological activity, makes it unlikely that kinetensin plays a role as a circulating regulatory peptide. Nevertheless, since the putative kinetensin substrate circulates at microM concentrations, it is feasible that kinetensin is generated and metabolized at the target organ.
Gov't Doc #: 8213349
Type: Journal Article
Subjects: Animals
Blood Proteins.pharmacokinetics.pharmacology
In Vitro Techniques
Infusions, Intra-Arterial
Jugular Veins
Oligopeptides.administration & dosage.blood.pharmacokinetics.pharmacology
Pancreas.drug effects.secretion
Pancreatic Polypeptide.secretion
Appears in Collections:Journal articles

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