Molecular mechanism of production and removal of neurotransmitters.

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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.