Theanine, an ingredient of green tea, inhibits [3H]glutamine transport in neurons and astroglia in rat brain

J Neurosci Res. 2008 Jun;86(8):1846-56. doi: 10.1002/jnr.21637.


We have previously shown that theanine (=gamma-glutamylethylamide), an ingredient of green tea, has a protective effect against ischemic neuronal death in the hippocampal CA1 region of the gerbil brain without affecting ligand binding to ionotropic receptor subtypes of the neurotransmitter glutamate structurally related to theanine. The neurotransmitter pool of glutamate is thought to be fueled by the entry of the other structural analog glutamine (Gln) and subsequent cleavage by glutaminase. Although theanine did not inhibit [3H]glutamate accumulation, [3H]theanine was actively accumulated in a temperature-dependent and saturable manner in rat brain synaptosomal fractions. The accumulation of [3H]theanine was markedly inhibited by Gln in a concentration-dependent manner, whereas [3H]Gln accumulation was inhibited by theanine vice versa. Both [3H]theanine and [3H]Gln accumulations were decreased after the replacement of sodium chloride with choline chloride, along with similarly high distribution profiles in telencephalic structures. A similar equilibrium was observed within 30 min at 30 degrees C for the accumulations of both [3H]theanine and [3H]Gln in cultured rat neocortical astroglia as well as neurons, whereas theanine inhibited [3H]Gln accumulation in a concentration-dependent manner at 0.1-10 mM. Furthermore, sustained exposure to 10 mM theanine led to a significant decrease in the level of extracellular glutamate released from cultured neurons. These results suggest that the green tea ingredient theanine would be an inhibitor of different transporters capable of transporting Gln across plasma membranes toward the modulation of the glutamate/Gln cycle required for the neurotransmitter pool of glutamate in neurons.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Biological Transport / drug effects
  • Biological Transport / physiology
  • Brain / drug effects
  • Brain / metabolism*
  • Cells, Cultured
  • Glutamates / pharmacology*
  • Glutamine / antagonists & inhibitors
  • Glutamine / metabolism*
  • Male
  • Neurons / drug effects
  • Neurons / metabolism*
  • Protein Binding / drug effects
  • Protein Binding / physiology
  • Rats
  • Rats, Wistar
  • Tea*
  • Tritium / metabolism


  • Glutamates
  • Tea
  • Glutamine
  • Tritium
  • theanine