Neurotensin metabolism in various tissues of central and peripheral origins: ubiquitous involvement of a novel neurotensin degrading metalloendopeptidase.
The metabolism of neurotensin in vitro, in various membrane preparations and cell lines of central and peripheral origins was studied. Neurotensin degradation products were separated by HPLC and identified by either amino acid analysis or by their retention times. Peptidases responsible for the cleavages were identified by means of specific fluorigenic substrates or inhibitors. Although the patterns of neurotensin inactivation varied according to the tissue source in all cases, a major primary cleavage occurred at the Pro10-Tyr11 bond, leading to the biologically inactive fragments NT1-10 and NT11-13. A novel neurotensin-degrading metallopeptidase was responsible for this cleavage. Interestingly, it was the only peptidase that was ubiquitously detected. In addition, endopeptidase 24.11 (EC 3.4.24.11) contributed to this cleavage in rat brain synaptic membranes as well as in circular and longitudinal smooth muscle plasma membranes from dog ileum.
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D004285:Dogs; D007082:Ileum / Q000201:enzymology; D007700:Kinetics; D008666:Metalloendopeptidases / Q000378:metabolism*; D009130:Muscle, Smooth / Q000201:enzymology; D009474:Neurons / Q000201:enzymology; D009496:Neurotensin / Q000378:metabolism*; D009928:Organ Specificity; D051381:Rats; D013379:Substrate Specificity; D013570:Synaptic Membranes / Q000201:enzymology
D009496:Neurotensin; D008666:Metalloendopeptidases