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. |