ROLE OF ENDOPEPTIDASE-3.4.24.16 IN THE CATABOLISM OF NEUROTENSIN, IN-VIVO, IN THE VASCULARLY PERFUSED DOG ILEUM

1 Tile degradation of tritiated and unlabelled neurotensin (NT) follow ing close intra-arterial infusion of the peptides in ileal segments of anaesthetized dogs was examined. 2 Intact NT and its catabolites reco vered in the venous effluents were purified by chromatography on Sep-P ak columns followed by reverse-phase h.p.l.c. and identified by their retention times or by radioimmunoassay. 3 The half-life of neurotensin was estimated to be between 2 and 6 min. Four labelled catabolites, c orresponding to free tyrosine, neurotensin (1-8), neurotensin (1-10) a nd neurotensin (1-11), were detected. 4 Neurotensin (1-11) was mainly generated by a phosphoramidon-sensitive cleavage, probably elicited by endopeptidase 24-11. 5 Two endopeptidase 3.4.24.16 inhibitors, phosph odiepryl 03 and the dipeptide Pro-Ile, dose-dependently potentiated th e recovery of intact neurotensin. Furthermore, both agents inhibited t he formation of neurotensin (1-10), the product that results from the hydrolysis of neurotensin by purified endopeptidase 3.4.24.16. In cont rast, the endopeptidase 3.4.24.15 inhibitor Cpp-AAY-pAB neither protec ted neurotensin from degradation nor modifed the production of neurote nsin (1-10). 6 Our study is the first evidence to indicate that endope ptidase 3.4.24.16 contributes to the catabolism of neurotensin, in viv o, in the dog intestine.