Glutamate transporters activities

Nakagawa, T., Fujio, M., Ozawa, T., Minami, M., Satoh, M. Effect of MS-153, a glutamate transporter activator, on the conditioned rewarding effects of morphine, methamphetamine and cocaine in mice. 

Winter S, Brunk I, Walther DJ, Holtje M, Jiang M, Peter JU, Takamori S, Jahn R, Birnbaumer L, hnert-Hilger G (2005) Galphao2 regulates vesicular glutamate transporter activity by changing its chloride dependence. J Neurosci 25 4672 1680. 

Chan H, Pannunzio M, Hazell AS, et al. 2001. Exposure to ammonia results in decreased glutamate transporter activity in cultured cerbellar granule cells. J Neurochem 78(Suppl 1) 40. 

Complementary to the work of Leighton, Kobayashi reported on the Zirconium-catalyzed enantioselective synthesis of the enantiomer of the neuroprotecting agent MS-153 (76, Scheme 41.16), ° a glutamate transporter activator discovered by Mitsui Toatsu Chemicals (Tokyo, Japan). The active catalyst was prepared by adding Zr(OPr)4 (20 mol%) to a suspension of 3,3 -l2Binol 73... 

Synaptic vesicles isolated from brain exhibit four distinct vesicular neurotransmitter transport activities one for monoamines, a second for acetylcholine, a third for the inhibitory neurotransmitters GABA and glycine, and a fourth for glutamate [1], Unlike Na+-dependent plasma membrane transporters, the vesicular activities couple to a proton electrochemical gradient (A. lh+) across the vesicle membrane generated by the vacuolar H+-ATPase ( vacuolar type proton translocating ATPase). Although all of the vesicular transport systems rely on ApH+, the relative dependence on the chemical and electrical components varies (Fig. 1). The... 

Dingledine, R et al. (1999) The glutamate receptor ion channels. Pharmacol. Rev. 51 7-61. Frerking, M and Nicoll, RA (2000) Synaptic kainate receptors. Curr. Opin. Neurobiol. 10 342-351. Gegelashvili, G and Schousboe, A (1997) High affinity glutamate transporters regulation of expression and activity. Mol. Pharmacol. 52 6-15. 

Excitotoxicity (see Chs 15 and 32) has been suggested to be a mechanism by which motor neurons are damaged in ALS [25,48,49]. About 60-70% of sporadic ALS patients have a 30-95% reduction in the levels of the astroglial glutamate transporter EAAT2 (excitatory amino acid transporter 2), also termed GLT-1, in motor cortex and spinal cord [25, 48, 49]. Reduction in level of activity of this major glutamate transporter leads to increased extracellular concentrations of glutamate at synapses and evidence of excitotoxicity exists in some patients with ALS. 

Borre, L. and Kanner, B. I. (2001) Coupled, but not uncoupled, fluxes in a neuronal glutamate transporter can be activated by lithium ions. J. Biol. Chem. 276,40396-40401. 

Fig. 2. Schematic diagram of the stoichometry of ion flux coupling and the chloride channel activity of glutamate transporters. Glutamate is coupled to the co-transport of 3 Na+, 1K+, and the countertransport of 1 K+. In addition, glutamate and Na+ binding to the transporter activates an uncoupled chloride flux through the transporter.

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