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Molecular mechanism of production and removal of neurotransmitters.

神经递质产生和去除的分子机制。

基本信息

批准号：
07308053
负责人：
TOHYAMA Masaya
金额：
$ 13.44万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

To examine the types of osmolite transporters involved in cytophylactic mechanisms in response to osmotic changes in the CNS,we analyzed the cerebral localization and the genetic expression of a number of transporter molecules including Myoinositol, an osmolite transporter, Betaine, Taurine and Glutamic acid transporters in an animal model of dehydration using ISH and northern blotting techniques. Myoinositol transporter was found to be the most expressed in the brain and its genetic expression shown to be regulated by blood serum osmotic pressure gradient.Moreover, in rat middle cerebral artery obstruction and in cerebral edema models, the increase of both the genetic expression and the transcription of myoinositol transporter was noticed not only in the lesion site, but was also widely extended to the peri-lesional area. Further, in osmotic pressure load models in the rat retina, an acute pressure load induced an increase of myoinositol transporter mRNA while a while a chronic pressure load to the retina selectively increased Taurine transporter mRNA.It is suggested from the above findings that the expression of osmolite transporter is differently regulated according to the kind of osmotic stimulus and to the lesion topography.Next, an attempt was made to isolate a new transporter molecule bearing osmotic pressure response. This experience resulted in the successful isolation of the cDNA and the demonstration of the primary structure of a new Peptide Histidine Transporter (PHT1) which is specifically expressed in the nervous system.Finally, from the study of a variety of expressions in the Xenopus oocytes, it was shown that carnosine, oligopeptides and histidine are transported in high affinity with the new transporter and in a proton-depended way.

为了研究渗透压转运蛋白的类型，参与细胞的渗透压机制，在中枢神经系统的渗透变化，我们分析了大脑的定位和遗传表达的一些转运蛋白分子，包括肌醇，渗透压转运蛋白，甜菜碱，牛磺酸和谷氨酸转运蛋白在脱水的动物模型，使用ISH和北方印迹技术。结果表明，肌醇转运体在脑组织中表达最高，其基因表达受血清渗透压梯度的调节，在大鼠大脑中动脉阻塞和脑水肿模型中，肌醇转运体基因表达和转录的增加不仅在损伤部位，而且广泛延伸至损伤周围。此外，在大鼠视网膜的渗透压负荷模型中，急性压力负荷诱导肌醇转运体mRNA的增加，而对视网膜的慢性压力负荷选择性地增加牛磺酸转运体mRNA。从上述发现可以看出，渗透压转运体的表达根据渗透刺激的种类和损伤地形而不同地调节。尝试分离具有渗透压响应的新转运蛋白分子。最后，通过对非洲爪蟾卵母细胞中多种表达的研究，发现肌肽、寡肽和组氨酸都与这种新的转运蛋白有很高的亲和力，并以质子依赖的方式转运。