Bare D J, Ghetti B, Richter J A
Department of Pathology, Indiana University School of Medicine, Indianapolis, USA.
J Neurochem. 1995 Nov;65(5):2096-104. doi: 10.1046/j.1471-4159.1995.65052096.x.
Protein tyrosine kinases that are known to have major roles in the control of cell growth and transformation are abundant and have numerous phosphoprotein substrates in the adult CNS. Although less well characterized than serine/threonine kinases, tyrosine kinases are also concentrated in the synapse. The effect of genistein, a selective inhibitor of tyrosine kinase activity, was examined on the in vitro release of endogenous dopamine (DA) from superfused mouse striatal slices. Fractional release of DA was significantly increased over basal release levels by genistein (100 and 200 microM). The effect was concentration dependent and rapidly reversible on washout of the kinase inhibitor. No significant change from basal release levels was observed with two structural analogues of genistein that do not inhibit tyrosine kinase activity at the same concentration. We have previously described alterations in basal and evoked DA release from the striatum of the weaver (wv/wv) mutant mouse, and genotypic differences in fractional release were also observed with genistein stimulation. The total evoked release was 25-50% greater from the wv/wv striatum. These results suggest a modulatory role for tyrosine kinase activity in neurotransmitter release and perhaps an alteration of kinase-regulated mechanisms in the DA-deficient wv/wv striatum.
已知在细胞生长和转化控制中起主要作用的蛋白质酪氨酸激酶在成体中枢神经系统中含量丰富且有众多磷蛋白底物。虽然酪氨酸激酶不如丝氨酸/苏氨酸激酶那样特征明确，但也集中在突触部位。研究了酪氨酸激酶活性的选择性抑制剂染料木黄酮对体外灌注的小鼠纹状体切片中内源性多巴胺（DA）释放的影响。染料木黄酮（100和200微摩尔）使DA的分数释放较基础释放水平显著增加。该效应呈浓度依赖性，且在激酶抑制剂洗脱后迅速可逆。与染料木黄酮结构类似但在相同浓度下不抑制酪氨酸激酶活性的两种物质，未观察到基础释放水平有显著变化。我们之前描述过织工（wv/wv）突变小鼠纹状体基础和诱发的DA释放的改变，染料木黄酮刺激时也观察到了分数释放的基因型差异。wv/wv纹状体诱发释放总量比正常纹状体高25% - 50%。这些结果表明酪氨酸激酶活性在神经递质释放中起调节作用，并且在DA缺乏的wv/wv纹状体中激酶调节机制可能发生了改变。
