In vivo inactivation of neurotensin in dog ileum: major involvement of endopeptidase 24-11.

The metabolism of tritiated neurotensin (NT) after close i.a. perfusion in ileal segments of anesthetized dog was studied. Venous effluents containing labeled metabolites and intact NT were collected and analyzed by high-performance liquid chromatography. The apparent half-life of the peptide was between 2 and 6 min. The tritiated metabolites of NT were identified as free tyrosine, NT-(1-7), NT-(1-8), NT-(1-10), NT-(11-13) and NT-(1-11). Pretreatment of dog ileum with thiorphan or captopril indicated that endopeptidase 24-11 inactivated NT by cleaving the peptide at the Pro10-Tyr11 and Tyr11-Ile12 bonds. Angiotensin-converting enzyme only participated in the secondary conversion of NT-(1-10) into NT-(1-8). The metabolisms of NT occurring in vivo and in vitro in central and peripheral organs are compared.