Neutral endopeptidase and alcohol consumption, experiments in neutral endopeptidase-deficient mice
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...
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Published in | European journal of pharmacology Vol. 397; no. 2; pp. 327 - 334 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Amsterdam
Elsevier B.V
02.06.2000
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | 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 (≈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 (≈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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0014-2999 1879-0712 |
DOI: | 10.1016/S0014-2999(00)00222-3 |