Phillis J W, Song D, O'Regan M H
Department of Physiology, Wayne State University, School of Medicine, Detroit, MI 48201, USA.
Neurosci Lett. 1996 Apr 5;207(3):151-4. doi: 10.1016/0304-3940(96)12521-0.
Protein tyrosine phosphorylation plays an important role in neuronal function. In this study we have examined the effects of inhibition of tyrosine phosphorylation on the extracellular levels of four neurotransmitter amino acids (aspartate, glutamate, gamma-aminobutyric acid (GABA) and glycine) and of the non-transmitter amino acid phosphoethanolamine during cerebral ischemia and reperfusion in a rat four vessel occlusion model. In comparison with the control group, the tyrosine kinase inhibitor genistein significantly depressed ischemia/reperfusion-evoked efflux of these amino acids, with the exception of GABA, into cerebral cortical superfusates. GABA efflux was non-significantly reduced. These results suggest that tyrosine phosphorylation is involved in the ischemia-evoked efflux of amino acids into the extracellular milieu, likely as a consequence of the phosphorylation of microtubule-associated protein kinase (MAP kinase) and downstream activation of PLA2 in the plasma membrane. Amino acid efflux would occur, in part, as a consequence of the ensuing disruption of plasma membrane integrity and leakage of cytoplasmic constituents along their concentration gradients.
蛋白质酪氨酸磷酸化在神经元功能中起重要作用。在本研究中，我们在大鼠四血管闭塞模型中，研究了酪氨酸磷酸化抑制对脑缺血和再灌注期间四种神经递质氨基酸（天冬氨酸、谷氨酸、γ-氨基丁酸（GABA）和甘氨酸）以及非递质氨基酸磷酸乙醇胺细胞外水平的影响。与对照组相比，酪氨酸激酶抑制剂染料木黄酮显著抑制了这些氨基酸（GABA除外）缺血/再灌注诱发的向大脑皮质灌流液中的流出。GABA流出减少但无统计学意义。这些结果表明，酪氨酸磷酸化参与了氨基酸缺血诱发的向细胞外环境的流出，这可能是微管相关蛋白激酶（MAP激酶）磷酸化以及质膜中PLA2下游激活的结果。氨基酸流出部分是由于随后质膜完整性的破坏以及细胞质成分沿其浓度梯度的泄漏所致。
