Abstract
Neutral endopeptidase EC 3.4.24.11 (NEP) is localized in peptidergic neurons and various colocalized peptides or other humoral mediators may serve as substrates. Target disruption of the NEP gene was reported to enhance the lethal response to endotoxin shock in mice. We examined thermonociceptive thresholds and enkephalin (ENK) tissue levels in transgenic NEP (-/-) and control wild type NEP (+/+) mice. Hot plate (52°C)latency was 13.1 ± 1.4 s in NEP (+/+) mice (n = 16) while latency increased significantly (P = 0.031) to 17.7 ± 1.6 s in NEP (-/-) mice. Naloxone (10 mg/kg) had no effect on hot plate latency in NEP (+/+) mice (12.5 s. n = 8), but significantly decreased the latency in NEP (-/-) mice compared to untreated NEP (-/-) deficient mice (10.5 s, n = 8). Morphine (3 or 10 mg/kg) analgesic response was similar in knockout mice and wild type mice. Methionine-ENK (MET-ENK) and leucine-ENK (LEU-ENK) levels were determined in extracts from cortex, brain stem, hypothalamus, striatum, spinal cord, trigeminal ganglion and heart in treated and untreated mice. ENK-levels varied in a regionally-dependent manner and were significantly decreased in hypothalamus and spinal cord. We conclude that deletion of the NEP gene results in an opioid-related increase in thermonociceptive threshold. Regional differences in opioid metabolism indicate that NEP evokes tissue-specific patterns of ENK-regulation. NEP selectively controls opioid biosynthesis in hypothalamus and spinal cord presumably by feedback regulation.
Original language | English |
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Pages (from-to) | 27-30 |
Number of pages | 4 |
Journal | Neuroscience Letters |
Volume | 234 |
Issue number | 1 |
DOIs | |
State | Published - Sep 26 1997 |
Bibliographical note
Funding Information:This study was supported by the Austrian Science Funds (F00206) and by NIH grant DA 06204. A.S. was a recipient of a Fulbright fellowship. The technical assistance of Iris Berger and Astrid Saria is acknowledged.
Keywords
- Enkephalin levels
- Enkephalinase
- Hot plate test
- Knockout mice
- Neutral endopeptidase
- Thermonociceptive threshold
ASJC Scopus subject areas
- General Neuroscience