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 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.
Siems
W
W
Institute of Molecular Pharmacology, Alfred-Kowalke-Str. 4, D-10315, Berlin, Germany.
Maul
B
B
Krause
W
W
Gerard
C
C
Hauser
K F
KF
Hersh
L B
LB
Fischer
H S
HS
Zernig
G
G
Saria
A
A
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
D004743:Enkephalin, Leucine; D018826:CD13 Antigens; D007703:Peptidyl-Dipeptidase A; D015260:Neprilysin