Volterra A, Trotti D, Cassutti P, Tromba C, Galimberti R, Lecchi P, Racagni G
Center of Neuropharmacology, University of Milan, Italy.
Adv Exp Med Biol. 1992;318:147-58. doi: 10.1007/978-1-4615-3426-6_13.
Recent evidence indicates that arachidonic acid (AA) and its metabolites play a fast messenger role in synaptic modulation in the CNS. 12-Lipoxygenase derivatives are released by Aplysia sensory neurons in response to inhibitory transmitters and directly target a class of K+ channels, increasing the probability of their opening. In this way, hyperpolarization is achieved and action potentials are shortened, leading to synaptic depression. Other types of K+ channels in vertebrate excitable cells have been found to be sensitive to arachidonic acid, lipoxygenase products, and polyunsaturated fatty acids (PUFA). In the mammalian CNS, arachidonic acid is released upon stimulation of N-methyl-D-aspartate (NMDA)-type glutamate receptors. We found that arachidonic acid inhibits the rate of glutamate uptake in both neuronal synaptic terminals and astrocytes. Neither biotransformation nor membrane incorporation are required for arachidonic acid to exert this effect. The phenomenon, which is rapid and evident at low microM concentrations of AA, may involve a direct interaction with the glutamate transporter or its lipidic microenvironment on the outer side of the cell membrane. Polyunsaturated fatty acids mimic arachidonate with a rank of potency parallel to the degree of unsaturation. Since the effect of glutamate on the synapses is terminated by diffusion and uptake, a slowing of the termination process may potentiate glutamate synaptic efficacy. However, excessive extracellular accumulation of glutamate may lead to neurotoxicity.
最近的证据表明，花生四烯酸（AA）及其代谢产物在中枢神经系统的突触调制中发挥快速信使作用。12-脂氧合酶衍生物由海兔感觉神经元响应抑制性递质而释放，并直接作用于一类钾离子通道，增加其开放的概率。通过这种方式，实现超极化并缩短动作电位，导致突触抑制。已发现脊椎动物可兴奋细胞中的其他类型钾离子通道对花生四烯酸、脂氧合酶产物和多不饱和脂肪酸（PUFA）敏感。在哺乳动物中枢神经系统中，花生四烯酸在N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体受刺激时释放。我们发现花生四烯酸抑制神经元突触终末和星形胶质细胞中谷氨酸的摄取速率。花生四烯酸发挥这种作用既不需要生物转化也不需要膜整合。这种现象在低 microM浓度的AA时迅速且明显，可能涉及与细胞膜外侧的谷氨酸转运体或其脂质微环境的直接相互作用。多不饱和脂肪酸以与不饱和度程度平行的效力等级模拟花生四烯酸盐。由于谷氨酸对突触的作用通过扩散和摄取而终止，终止过程的减慢可能增强谷氨酸的突触效力。然而，谷氨酸在细胞外的过度积累可能导致神经毒性。
