Inactivation of neurotensin by rat brain synaptic membranes. Cleavage at the Pro10-Tyr11 bond by endopeptidase 24.11 (enkephalinase) and a peptidase different from proline-endopeptidase

J Neurochem. 1984 Nov;43(5):1295-301. doi: 10.1111/j.1471-4159.1984.tb05386.x.


It was shown previously that the tridecapeptide neurotensin is inactivated by rat brain synaptic membranes and that one of the primary inactivating cleavages occurs at the Pro10-Try11 peptide bond, leading to the formation of NT1-10 and NT11-13. The present study was designed to investigate the possibility that this cleavage was catalyzed by proline endopeptidase and/or endopeptidase 24.11 (enkephalinase). Purified rat brain synaptic membranes were found to contain a N-benzyloxycarbonyl-Gly-Pro-4-methyl-coumarinyl-7-amide-hydrolyzin g activity that was markedly inhibited (93%) by the proline endopeptidase inhibitor N-benzyloxycarbonyl-Pro-Prolinal and partially blocked (25%) by an antiproline endopeptidase antiserum. In contrast, the cleavage of neurotensin at the Pro10-Tyr11 bond by synaptic membranes was not affected by N-benzyloxycarbonyl-Pro-Prolinal and the antiserum. When the conversion of NT1-10 to NT1-8 by angiotensin converting enzyme was blocked by captopril and when the processing of NT11-13 by aminopeptidase(s) was inhibited by bestatin, it was found that thiorphan, a potent endopeptidase 24.11 inhibitor, partially decreased the formation of NT1-10 and NT11-13 by synaptic membranes.

In conclusion: (1) proline endopeptidase, although it is present in synaptic membranes, is not involved in the cleavage of neurotensin at the Pro10-Tyr11 bond; (2) endopeptidase 24.11 only partially contributes to this cleavage; (3) there exists in rat brain synaptic membranes a peptidase different from proline endopeptidase and endopeptidase 24.11 that is mainly responsible for inactivating neurotensin by cleaving at the Pro10-Tyr11 bond.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Captopril / pharmacology
  • Dipeptides / pharmacology
  • Endopeptidases / metabolism*
  • Hydrolysis
  • Leucine / analogs & derivatives
  • Leucine / pharmacology
  • Neprilysin
  • Neurotensin / antagonists & inhibitors
  • Neurotensin / metabolism*
  • Peptide Fragments / metabolism
  • Peptide Hydrolases / metabolism*
  • Proline / metabolism
  • Prolyl Oligopeptidases
  • Rats
  • Serine Endopeptidases*
  • Synaptic Membranes / drug effects
  • Synaptic Membranes / enzymology*
  • Thiorphan
  • Tiopronin / analogs & derivatives
  • Tiopronin / pharmacology
  • Tyrosine / metabolism


  • Dipeptides
  • Peptide Fragments
  • Neurotensin
  • Tyrosine
  • N-benzyloxycarbonylprolylprolinal
  • Proline
  • Captopril
  • Thiorphan
  • Tiopronin
  • Endopeptidases
  • Peptide Hydrolases
  • Serine Endopeptidases
  • Prolyl Oligopeptidases
  • Neprilysin
  • Leucine
  • ubenimex