title: Neutral endopeptidase and alcohol consumption, experiments in neutral endopeptidase-deficient mice.
abstract: Alcohol consumption was investigated in mice which were rendered deficient in the peptide-degrading enzyme neutral endopeptidase (EC 3.4.24.11) (NEP-/-) by gene targeting and compared to alcohol consumption in corresponding wild type mice (NEP+/+). Mice were offered a free choice to drink tap water or 10% alcohol. The NEP-/- mice consumed significantly more alcohol ( approximately 42%) than the NEP+/+ mice, whereas no significant differences were observed in the total fluid consumption. The daily food consumption of alcohol naive NEP-/- animals was elevated ( approximately 29%). Furthermore, the activities of peptidases closely related to neutral endopeptidase were analysed ex vivo in several brain regions from NEP-/- and NEP+/+ mice not treated with alcohol. There was no obvious compensation for the total loss of neutral endopeptidase by the functionally related peptidases angiotensin-converting enzyme and aminopeptidase N. In vitro, the degradation of exogenously applied [Leu(5)]enkephalin was not reduced in membrane preparations of those brain regions assayed in NEP-/- mice. A small reduction in [Leu(5)]enkephalin degradation was detected in striatal membrane preparations of NEP-/- mice, if aminopeptidase N was additionally blocked by bestatin or amastatin.
authors.affiliation: Institute of Molecular Pharmacology, Alfred-Kowalke-Str. 4, D-10315, Berlin, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Siems
authors.forename: B
authors.initials: B
authors.lastname: Maul
authors.forename: W
authors.initials: W
authors.lastname: Krause
authors.forename: C
authors.initials: C
authors.lastname: Gerard
authors.forename: K F
authors.initials: KF
authors.lastname: Hauser
authors.forename: L B
authors.initials: LB
authors.lastname: Hersh
authors.forename: H S
authors.initials: HS
authors.lastname: Fischer
authors.forename: G
authors.initials: G
authors.lastname: Zernig
authors.forename: A
authors.initials: A
authors.lastname: Saria
mesh_terms: D000428:Alcohol Drinking; D000818:Animals; D001303:Auditory Cortex / Q000378:metabolism; D001921:Brain / Q000201:enzymology; D018826:CD13 Antigens / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004743:Enkephalin, Leucine / Q000378:metabolism; D005838:Genotype; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000378:metabolism; D008636:Mesencephalon / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D015260:Neprilysin / Q000235:genetics / Q000378:metabolism*; D009830:Olfactory Bulb / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D013788:Thalamus / Q000378:metabolism
chemical_list: D004743:Enkephalin, Leucine; D018826:CD13 Antigens; D007703:Peptidyl-Dipeptidase A; D015260:Neprilysin