Chronic ethanol increases N-methyl-D-aspartate-stimulated nitric oxide formation but not receptor density in cultured cortical neurons

被引:106
作者
Chandler, LJ
Sutton, G
Norwood, D
Sumners, C
Crews, FT
机构
[1] UNIV FLORIDA, COLL MED, DEPT PHYSIOL, GAINESVILLE, FL 32610 USA
[2] UNIV N CAROLINA, BOWLES CTR ALCOHOL STUDIES, CHAPEL HILL, NC 27599 USA
关键词
D O I
10.1124/mol.51.5.733
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The effects of prolonged ethanol exposure on excitatory amino acid receptor stimulated nitric oxide (NO) formation were examined in primary rat cortical neuronal cultures. Chronic ethanol (4 days, 100 mM) potentiated N-methyl-D-aspartate (NMDA)-stimulated NO formation as determined by measuring the conversion of [H-3]arginine to [H-3]citrulline. In contrast, chronic ethanol had no effect on NO formation stimulated by kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxalonepropionic acid, or the calcium ionophore ionomycin. Potassium chloride-stimulated NO formation was also enhanced by chronic ethanol treatment, but this effect was not seen in the presence of the ionotropic glutamate receptor antagonists MK-801 and 6-cyano-7-nitroquinoxaline-2,3-dione. Immunoblot analysis of expression of NR1, NR2A, and NR2B receptor subunits showed no difference between control and chronic ethanol-treated cultures. In support of this apparent lack of change in receptor density, there was no difference in the specific binding of I-125-MK-801 between control and chronic ethanol-treated groups. These results demonstrate that prolonged ethanol exposure selectively enhanced NMDA receptor-stimulated NO formation, which may play an important role in alcohol dependence, withdrawal, and alcohol-associated brain damage. These results also suggest that chronic ethanol-induced increases in NMDA receptor function may not be due to a simple increase in the number of NMDA receptors or change in NMDA receptor subunit composition but may instead reflect more complicated and subtle changes.
引用
收藏
页码:733 / 740
页数:8
相关论文
共 40 条
[21]   INFLUENCE OF NITRIC-OXIDE SYNTHASE INHIBITION ON THE DEVELOPMENT OF RAPID TOLERANCE TO ETHANOL [J].
KHANNA, JM ;
MORATO, GS ;
CHAU, A ;
SHAH, G .
BRAIN RESEARCH BULLETIN, 1995, 37 (06) :599-604
[22]   HOMOMERIC ASSEMBLIES OF NMDAR1 SPLICE VARIANTS ARE SENSITIVE TO ETHANOL [J].
KOLTCHINE, V ;
ANANTHARAM, V ;
WILSON, A ;
BAYLEY, H ;
TREISTMAN, SN .
NEUROSCIENCE LETTERS, 1993, 152 (1-2) :13-16
[23]   CLONING OF CDNA FOR THE GLUTAMATE-BINDING SUBUNIT OF AN NMDA RECEPTOR COMPLEX [J].
KUMAR, KN ;
TILAKARATNE, N ;
JOHNSON, PS ;
ALLEN, AE ;
MICHAELIS, EK .
NATURE, 1991, 354 (6348) :70-73
[24]   CLEAVAGE OF STRUCTURAL PROTEINS DURING ASSEMBLY OF HEAD OF BACTERIOPHAGE-T4 [J].
LAEMMLI, UK .
NATURE, 1970, 227 (5259) :680-+
[25]   REGULATION OF NMDA CHANNEL FUNCTION BY ENDOGENOUS CA2+-DEPENDENT PHOSPHATASE [J].
LIEBERMAN, DN ;
MODY, I .
NATURE, 1994, 369 (6477) :235-239
[26]   THE COMPETITIVE NMDA RECEPTOR ANTAGONIST, CGP-39551, INHIBITS ETHANOL WITHDRAWAL SEIZURES [J].
LILJEQUIST, S .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1991, 192 (01) :197-198
[27]  
MASOOD K, 1994, MOL PHARMACOL, V45, P324
[28]  
MONCADA S, 1993, NEW ENGL J MED, V329, P2002
[29]   MK-801 POTENTLY INHIBITS ALCOHOL-WITHDRAWAL SEIZURES IN RATS [J].
MORRISETT, RA ;
REZVANI, AH ;
OVERSTREET, D ;
JANOWSKY, DS ;
WILSON, WA ;
SWARTZWELDER, HS .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1990, 176 (01) :103-105
[30]   MOLECULAR DIVERSITY OF GLUTAMATE RECEPTORS AND IMPLICATIONS FOR BRAIN-FUNCTION [J].
NAKANISHI, S .
SCIENCE, 1992, 258 (5082) :597-603