Premium
Nitric Oxide Synthase Activity Endogenously Modulates NMDA Receptors
Author(s) -
Manzoni Olivier,
Bockaert Joel
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb03580.x
Subject(s) - nmda receptor , nitric oxide synthase , nitric oxide , arginine , receptor , chemistry , glutamate receptor , endogeny , biochemistry , nitroarginine , endocrinology , medicine , biology , amino acid
We tested the possibility that endogenous nitric oxide synthase activity regulated NMDA receptors in primary cultured striatal neurons. We monitored NMDA‐induced increase in intra‐cellular Ca 2+ levels with fura‐2 ratio imaging, while nitric oxide synthase activity was either increased with l ‐arginihe (the natural substrate of nitric oxide synthase) or inhibited using nitro‐ l ‐arginine (a specific inhibitor of nitric oxide synthase). We found that the NMDA receptor effect was slowly but strongly diminished after an l ‐arginine (1 m M , 15 min) treatment ( l ‐arginine preincubation reduced the 100 μM NMDA‐induced maximal effect by 30–50%). The l ‐arginine blockade of NMDA receptors was long‐lasting but could be partially reversed by hemoglobin (100 μM , 10 min), which binds nitric oxide. This was not observed when the neurons were treated with l ‐arginine together with nitro‐ l ‐arginine. Our data strongly suggest that physiological nitric oxide synthase activity could regulate NMDA receptors.