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Publication : Neutral endopeptidase and alcohol consumption, experiments in neutral endopeptidase-deficient mice.

First Author  Siems W Year  2000
Journal  Eur J Pharmacol Volume  397
Issue  2-3 Pages  327-34
PubMed ID  10844131 Mgi Jnum  J:102814
Mgi Id  MGI:3608097 Doi  10.1016/s0014-2999(00)00222-3
Citation  Siems W, et al. (2000) Neutral endopeptidase and alcohol consumption, experiments in neutral endopeptidase-deficient mice. Eur J Pharmacol 397(2-3):327-34
abstractText  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.
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