Role of endopeptidase 126.96.36.199 in the catabolism of neurotensin, in vivo, in the vascularly perfused dog ileum
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1. The degradation of tritiated and unlabelled neurotensin (NT) following close intra-arterial infusion of the peptides in ileal segments of anaesthetized dogs was examined. 2. Intact NT and its catabolites recovered in the venous effluents were purified by chromatography on Sep-Pak 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, corresponding to free tyrosine, neurotensin (1-8), neurotensin (1-10) and 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 188.8.131.52 inhibitors, phosphodiepryl 03 and the dipeptide Pro-Ile, dose-dependently potentiated the recovery of intact neurotensin. Furthermore, both agents inhibited the formation of neurotensin (1-10), the product that results from the hydrolysis of neurotensin by purified endopeptidase 184.108.40.206. In contrast, the endopeptidase 220.127.116.11 inhibitor Cpp-AAY-pAB neither protected neurotensin from degradation nor modified the production of neurotensin (1-10). 6. Our study is the first evidence to indicate that endopeptidase 18.104.22.168 contributes to the catabolism of neurotensin, in vivo, in the dog intestine.