Waseem Tatyana V, Lapatsina Liudmila P, Fedorovich Sergei V
Institute of Biophysics and Cell Engineering, Akademicheskaya St., 27, Minsk 220072, Belarus.
Neurochem Res. 2008 Jul;33(7):1316-24. doi: 10.1007/s11064-007-9585-5. Epub 2008 Feb 13.
Polyvalent cations and hypertonic shrinking of presynaptic endings lead to calcium-independent exocytosis in various synapses. In the present study we have investigated the contribution of integrins to this phenomenon. It was found that hypertonic shrinking, polyvalent cations ruthenium red and gadolinium results in dose-dependent calcium-independent neurotransmitter release in rat brain synaptosomes. The exocytotic mechanism of neurotransmitter release induced by 300 microM gadolinium was additionally verified by the fluorescent dye FM2-10. We found that 200 microM of RGDS peptide, an inhibitor of integrins, decreased polyvalent gadolinium-induced [3H]D: -aspartate release by 26%. This compound had no effect upon hypertonicity-induced release. The peptide RGES, a negative control for RGDS; genistein, an inhibitor of tyrosine kinases; and citrate, an inhibitor of lanthanides-induced aggregation were ineffective in both cases. Therefore, we have shown that integrins did not influence hypertonicity-evoked [3H]D: -aspartate release, but partially mediated that evoked by gadolinium ions.
多价阳离子和突触前末梢的高渗性收缩会导致各种突触中出现不依赖钙的胞吐作用。在本研究中,我们调查了整合素对这一现象的作用。研究发现,高渗性收缩、多价阳离子钌红和钆会导致大鼠脑突触体中出现剂量依赖性的不依赖钙的神经递质释放。用荧光染料FM2-10进一步验证了由300微摩尔钆诱导的神经递质释放的胞吐机制。我们发现,200微摩尔的RGDS肽(一种整合素抑制剂)可使多价钆诱导的[3H]D-天冬氨酸释放减少26%。该化合物对高渗诱导的释放没有影响。RGES肽是RGDS的阴性对照;染料木黄酮是酪氨酸激酶的抑制剂;柠檬酸盐是镧系元素诱导聚集的抑制剂,在这两种情况下均无效。因此,我们表明整合素不影响高渗诱发的[3H]D-天冬氨酸释放,但部分介导了钆离子诱发的释放。