title: Effects of thiorphan, bestatin and a novel metallopeptidase inhibitor JMV 390-1 on the recovery of neurotensin and neuromedin N released from mouse hypothalamus.
abstract: The effects of the endopeptidase 24.11 ('enkephalinase') inhibitor thiorphan, the aminopeptidase inhibitor bestatin and a novel metallopeptidase inhibitor JMV 390-1 on the K(+)-evoked release of immunoreactive neurotensin and neuromedin N (iNT and iNN) from mouse hypothalamic slices were examined. (JMV 390-1 inhibits several metallopeptidases including endopeptidases 24.11, 24.15 and 24.16, and aminopeptidase N equipotently with Ki values around 50 nM.) Thiorphan increased the recovery of released iNT nearly 2-fold and had no effect on iNN. Bestatin produced a 4-fold increase in iNN recovery and was inactive on iNT. Finally, iNT and iNN recoveries were increased up to 4- and 5-fold, respectively, by JMV 390-1. These results show that in the mouse hypothalamus endopeptidase 24.11 participates with other metalloendopeptidases to the degradation of endogenously released NT while endogenously released NN is principally degraded by aminopeptidase(s).
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire du CNRS, Sophia Antipolis, Valbonne, France.
authors.forename: P
authors.initials: P
authors.lastname: Kitabgi
authors.forename: I
authors.initials: I
authors.lastname: Dubuc
authors.forename: D
authors.initials: D
authors.lastname: Nouel
authors.forename: J
authors.initials: J
authors.lastname: Costentin
authors.forename: J C
authors.initials: JC
authors.lastname: Cuber
authors.forename: H
authors.initials: H
authors.lastname: Fulcrand
authors.forename: S
authors.initials: S
authors.lastname: Doulut
authors.forename: M
authors.initials: M
authors.lastname: Rodriguez
authors.forename: J
authors.initials: J
authors.lastname: Martinez
mesh_terms: D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000818:Animals; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D066298:In Vitro Techniques; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D051379:Mice; D008969:Molecular Sequence Data; D015260:Neprilysin / Q000037:antagonists & inhibitors; D009496:Neurotensin / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D015244:Thiorphan / Q000494:pharmacology*
chemical_list: D009842:Oligopeptides; D010446:Peptide Fragments; C042090:neuromedin N; C078372:JMV 390-1; D009496:Neurotensin; D015244:Thiorphan; D000626:Aminopeptidases; D008666:Metalloendopeptidases; D015260:Neprilysin; D007930:Leucine; C012211:ubenimex; D011188:Potassium