Molecular mechanism of production and removal of neurotransmitters.

为了研究参与中枢神经系统渗透变化的细胞降解机制的渗透石转运体类型，我们使用ISH和northern blotting技术分析了脱水动物模型中肌醇、渗透石转运体、甜菜碱、牛磺酸和谷氨酸转运体等多种转运体分子的大脑定位和遗传表达。肌醇转运蛋白在大脑中表达最多，其基因表达受血清渗透压梯度的调节。此外，在大鼠大脑中动脉阻塞和脑水肿模型中，肌醇转运蛋白的基因表达和转录的增加不仅出现在病变部位，而且广泛扩展到病变周围区域。此外，在大鼠视网膜渗透压负荷模型中，急性压力负荷诱导肌醇转运蛋白mRNA增加，而视网膜慢性压力负荷选择性地增加牛磺酸转运蛋白mRNA。综上所述，渗透石转运体的表达受渗透刺激种类和病变地形的不同而有不同的调控。接下来，尝试分离一种新的具有渗透压响应的转运蛋白分子。这一经验导致了cDNA的成功分离和一个新的肽组氨酸转运蛋白（PHT1）的初级结构的展示，该蛋白在神经系统中特异性表达。最后，通过对非洲爪蟾卵母细胞中多种表达的研究表明，肌肽、寡肽和组氨酸与新的转运体具有高亲和力，并以质子依赖的方式进行转运。

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.