Molecular pharmacology of the Na+-dependent transport of acidic amino acids in the mammalian central nervous system

Biological & Pharmaceutical Bulletin
V J Balcar

Abstract

The Na+-dependent transport of L-glutamate (GluT) has been identified in brain tissue more than thirty years ago. Neurochemical studies, performed in various experimental models during 1970's, defined the basic rules for the selection or synthesis of GluT-specific substrates and inhibitors. The protein molecules (transporters) that mediate the translocation of the substrates across the plasma membrane have been cloned and studied during the last ten years. The sites on the transporters that bind the substrates favour glutamate-like or aspartate-like molecules with one positively charged and two negatively charged ionised groups. Substituents at C3 and C4 are often tolerated but substitutions at C2 or alterations of the ionisable groups usually impede the binding. The substrate binding sites display an "anomalous" selectivity towards stereoisomers. These structural requirements are shared by all Na+-dependent glutamate transporters thus making the design of transporter-selective ligands a challenging task. Moreover, the molecular mechanisms of the transport have not yet been adequately elucidated. Data from a wide variety of experimental studies strongly indicate that Na+-dependent GluT regulates the functioning of the glutamate...Continue Reading

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Citations

Oct 18, 2005·Journal of Biomedical Science·Ellas K NanitsosVladimir J Balcar
Sep 8, 2010·The Journal of Physiology·Trent R AndersonDavid A Prince
Sep 25, 2004·Glia·Angelika BröerStefan Bröer
Sep 16, 2009·Neurochemistry International·Karen Renata Matos OliveiraJosé Luiz Martins do Nascimento
May 17, 2007·Journal of Neurochemistry·Stefan BröerCaroline Rae
Nov 7, 2006·Journal of Neuroscience Research·Charbel E-H MoussaVladimir J Balcar
Nov 8, 2006·British Journal of Pharmacology·P M Beart, R D O'Shea
Jun 24, 2004·Brain Research. Brain Research Reviews·Yasushi ShigeriKeiko Shimamoto
Jun 4, 2015·Stress : the International Journal on the Biology of Stress·María Mercedes OdeonGabriela Beatriz Acosta
May 17, 2011·The Biochemical Journal·Stefan Bröer, Manuel Palacín
Jun 20, 2008·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Keiko Shimamoto
Feb 18, 2006·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Vladimir J Balcar, Ellas K Nanitsos
Jan 6, 2005·The Journal of Biological Chemistry·Marie-Pierre Hasne, Buddy Ullman
Nov 30, 2004·Clinical and Experimental Pharmacology & Physiology·Ellas K NanitsosVladimir J Balcar

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