Saransaari P, Oja S S
Tampere Brain Research Center, Medical School, University of Tampere, Tampere, Finland.
Amino Acids. 2004 Feb;26(1):91-8. doi: 10.1007/s00726-003-0004-1. Epub 2003 May 9.
The release of the inhibitory neuromodulator taurine in the hippocampus is markedly enhanced under various neural cell-damaging conditions, including ischemia and exposure to free radicals. The properties and regulation of the release evoked by a medium containing free radicals was investigated in hippocampal slices from adult (3-month-old) and developing (7-day-old) mice, using a superfusion system. The 'free radical damage' was induced by applying 0.01% H(2)O(2). The release of [(3)H]taurine was in both adult and developing hippocampus partly Ca(2+)-independent, mediated by Na(+)-dependent transporters and probably resulting from disruption of cell membranes and subsequent ion imbalance. The release in developing mice appeared to be more susceptible to regulation than that in adults, the stimulation by free radicals being in the latter already maximal. The release was reduced by adenosine A(1) receptor agonist R(-)N(6)-(2-phenylisopropyl)adenosine, which effect was, however, abolished by the antagonist 8-cyclopentyl-1,3-dipropylxanthine only in the immature hippocampus, indicating a receptor-mediated process. Moreover, the evoked taurine release in developing mice was potentiated by the ionotropic glutamate receptor agonists N-methyl-D-aspartate, kainate and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate in a receptor-mediated manner, since the effects were abolished by their respective antagonists. The metabotropic glutamate receptors are of only minor significance in the release, the agonists of group I and II receptors slightly reducing the release. Furthermore, NO may also be involved in this release, the NO-generating compounds hydroxylamine and S-nitroso-N-acetylpenicillamine being able to enhance the free-radical-evoked release. It seems that the free-radical-stimulated release, potentiated by ionotropic glutamate receptor activation and NO production, could constitute part of the neuroprotective properties of taurine, being important particularly in the developing hippocampus and hence preventing excitotoxicity.
在包括缺血和暴露于自由基等各种神经细胞损伤条件下，海马体中抑制性神经调质牛磺酸的释放会显著增强。利用灌流系统，研究了含有自由基的培养基诱发的释放特性及其调节机制，所用实验材料为成年（3个月大）和发育中（7天大）小鼠的海马切片。通过施加0.01%的H₂O₂诱导“自由基损伤”。成年和发育中海马体中[³H]牛磺酸的释放部分不依赖Ca²⁺，由Na⁺依赖性转运体介导，可能是细胞膜破坏及随后离子失衡所致。发育中小鼠的释放似乎比成年小鼠更容易受到调节，自由基对成年小鼠的刺激已经达到最大程度。腺苷A₁受体激动剂R(-)N₆-(2-苯异丙基)腺苷可减少释放，但拮抗剂8-环戊基-1,3-二丙基黄嘌呤仅在未成熟海马体中消除了该效应，表明这是一个受体介导的过程。此外，离子型谷氨酸受体激动剂N-甲基-D-天冬氨酸、 kainate和2-氨基-3-羟基-5-甲基-4-异恶唑丙酸以受体介导的方式增强了发育中小鼠诱发的牛磺酸释放，因为它们各自的拮抗剂消除了这些效应。代谢型谷氨酸受体在释放中作用较小，I组和II组受体的激动剂略微减少了释放。此外，NO也可能参与此释放过程，产生NO的化合物羟胺和S-亚硝基-N-乙酰青霉胺能够增强自由基诱发的释放。似乎由离子型谷氨酸受体激活和NO产生所增强的自由基刺激释放，可能构成牛磺酸神经保护特性的一部分，这在发育中的海马体中尤为重要，从而预防兴奋性毒性。
