Knapp D J, Crews F T
Center for Alcohol Studies and Department of Pharmacology, University of North Carolina, Chapel Hill 27599-7178, USA.
Alcohol Clin Exp Res. 1999 Apr;23(4):633-43.
Prostaglandins play an important role in the regulation of nervous system function including thermoregulation, autonomic nervous system function, hypothalamic regulation of pituitary function, and neuronal excitation. Prostaglandin synthesis is catalyzed by cyclooxygenase (COX; prostaglandin synthase) which occurs as two isozymes, COX-1 and COX-2. COX-1 and COX-2 are constitutively expressed in brain whereas COX-2 type is also inducible in brain by excitatory neurotransmission. Ethanol intoxication and the hyperexcitability of ethanol withdrawal may be influenced by inducible proteins, thus we investigated COX-2 in the rat brain during acute and chronic ethanol treatment, ethanol withdrawal, and after peripheral administration of excitatory amino acids. Kainic acid or NMDA treatment increased COX-2 immunoreactivity in the cortex, hippocampus, and amygdala. An acute dose of ethanol (5 g/kg, intragastric-i.g.) increased COX-2, particularly in the CA4 region of the hippocampus and agranular insular cortex. Chronic ethanol treatment (4 days-intragastric) robustly induced COX-2 in limbic cortex, isocortex, and amygdala. Particularly dense immunocytochemical staining was found in perirhinal and piriform cortices, dentate gyrus, and tenia tecta. During ethanol withdrawal, COX-2 expression increased further in some regions, peaking in most areas 16 hr after the last dose of ethanol. These results indicate that COX-2 immunoreactivity is: 1) increased in the brain during acute ethanol exposure that increases further during chronic treatment; 2) sensitive to excitatory amino acid receptor stimulation; and 3) dramatically increased during ethanol withdrawal. These studies suggest that COX-2 induction may be involved in the acute and chronic effects of ethanol.
前列腺素在神经系统功能调节中发挥着重要作用，包括体温调节、自主神经系统功能、下丘脑对垂体功能的调节以及神经元兴奋。前列腺素的合成由环氧化酶（COX；前列腺素合成酶）催化，该酶以两种同工酶COX - 1和COX - 2的形式存在。COX - 1和COX - 2在大脑中组成性表达，而COX - 2型也可通过兴奋性神经传递在大脑中被诱导。乙醇中毒和乙醇戒断后的过度兴奋可能受诱导蛋白影响，因此我们研究了急性和慢性乙醇处理、乙醇戒断期间以及外周给予兴奋性氨基酸后大鼠脑中的COX - 2。 kainic酸或NMDA处理增加了皮质、海马体和杏仁核中的COX - 2免疫反应性。急性剂量的乙醇（5 g/kg，胃内给药 - i.g.）增加了COX - 2，特别是在海马体的CA4区和无颗粒岛叶皮质。慢性乙醇处理（4天 - 胃内给药）强烈诱导边缘皮质、等皮质和杏仁核中的COX - 2。在嗅周皮质和梨状皮质、齿状回和带状回中发现特别密集的免疫细胞化学染色。在乙醇戒断期间，COX - 2表达在一些区域进一步增加，在最后一剂乙醇后16小时在大多数区域达到峰值。这些结果表明，COX - 2免疫反应性：1）在急性乙醇暴露期间大脑中增加，在慢性处理期间进一步增加；2）对兴奋性氨基酸受体刺激敏感；3）在乙醇戒断期间显著增加。这些研究表明，COX - 2的诱导可能参与乙醇的急性和慢性作用。
