期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 397, 期 2-3, 页码 327-334出版社
ELSEVIER
DOI: 10.1016/S0014-2999(00)00222-3
关键词
neutral endopeptidase; enkephalinase; enkephalin; knockout mouse; alcohol consumption; angiotensin-converting enzyme; enkephalin-degrading peptidases; opioid
资金
- NIDA NIH HHS [DA02243, DA06204] Funding Source: Medline
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 (approximate to 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 (approximate to 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. (C) 2000 Elsevier Science B.V. All rights reserved.
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