Methyl-beta-cyclodextrin but not retinoic acid reduces EAAT3-mediated glutamate uptake and increases GTRAP3-18 expression

J Neurochem. 2003 Feb;84(4):891-4. doi: 10.1046/j.1471-4159.2003.01588.x.

Abstract

The Na+-dependent glutamate transporter EAAT3 facilitates glutamate uptake into neurons as well as many other cell types. GTRAP3-18 (JWA, Arl6ip5) is a novel protein that interacts with EAAT3 and negatively modulates EAAT3-mediated glutamate uptake. Previous studies suggest that retinoic acid (RA) decreases Na+-dependent glutamate uptake and increases GTRAP3-18 protein expression. However, the RA used in those studies was complexed with methyl-beta-cyclodextrin (MebetaCD). In the present study we found that MebetaCD, but not RA, significantly reduced Na+-dependent EAAT3-mediated [3H]glutamate uptake in human embryonic kidney 293 (HEK293) cells. MebetaCD also significantly increased GTRAP3-18 protein expression in HEK293 cells as well as in rat hypothalamic neuron cultures. Intracerebroventricular administration of MebetaCD to the mouse brain resulted in a significant increase in GTRAP3-18 immunoreactivity in the hippocampus and cerebral cortex. In conclusion, we have shown that MebetaCD reduces EAAT3-mediated glutamate uptake and induces the expression of GTRAP3-18 protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport System X-AG / metabolism*
  • Animals
  • Carrier Proteins / metabolism*
  • Cell Line
  • Cells, Cultured
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cyclodextrins / administration & dosage
  • Cyclodextrins / pharmacology*
  • Excitatory Amino Acid Transporter 3
  • Glutamate Plasma Membrane Transport Proteins
  • Glutamic Acid / pharmacokinetics*
  • Heat-Shock Proteins
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Humans
  • Hypothalamus / cytology
  • Injections, Intraventricular
  • Kidney / cytology
  • Kidney / drug effects
  • Kidney / metabolism
  • Male
  • Membrane Transport Proteins
  • Mice
  • Mice, Inbred C57BL
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Sodium / metabolism
  • Symporters / metabolism*
  • Tretinoin / pharmacology*
  • beta-Cyclodextrins*

Substances

  • Amino Acid Transport System X-AG
  • Arl6ip5 protein, mouse
  • Carrier Proteins
  • Cyclodextrins
  • Excitatory Amino Acid Transporter 3
  • Glutamate Plasma Membrane Transport Proteins
  • Heat-Shock Proteins
  • Membrane Transport Proteins
  • SLC1A1 protein, human
  • Slc1a1 protein, mouse
  • Symporters
  • beta-Cyclodextrins
  • methyl-beta-cyclodextrin
  • Glutamic Acid
  • Tretinoin
  • Sodium