Inhibition by Theanine of Binding of [³H]AMPA, [³H]Kainate, and [³H]MDL 105,519 to Glutamate Receptors

Abstract

In an investigation of the mechanisms of the neuroprotective eŠects of theanine (g-glutamylethylamide) in brain ischemia, inhibition by theanine of the binding of [ 3 H](RS )-a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), [ 3 H]kainate, and [ 3 H]( E )-3-(2-phenyl-2-carboxyethenyl)-4,6-dichloro-1-H-indole-2-carboxylic acid (MDL 105,519) to glutamate receptors was studied in terms of its possible inhibiting eŠects on the three receptor subtypes (AMPA, kainate, and NMDA glycine), with rat cortical neurons. Theanine bound the three receptors, but its IC 50 of theanine was 80-to 30,000-fold less than that of L-glutamic acid.

Theanine, γ-glutamylethylamide, a unique amino acid in tea leaves, modulates neurotransmitter concentrations in the brain striatum interstitium in conscious rats

“…Moreover, because theanine did not change the glutamate level in the perfusate (Fig. 3a), theanine itself might have acted on AMPA/kainate receptors directly (Kakuda et al 2002a). …”

“…(Moghaddam et al 1990;Yadid et al 1993;Koga and Momiyama 2000). Because the chemical structure of theanine is similar to glutamic acid, some studies of theanine examined its relationship to glutamic acid function and metabolism (Sugiyama et al 2003;Kakuda et al 2002a;Tsuge et al 2003;Oda et al 1980); however, the glutamate receptor antagonist MK-801 did not affect the increase of dopamine concentration by theanine injection in the rat striatum (Yokogoshi et al 1998a). This result suggested that theanine did not affect glutamate neurotransmission.…”

“…In addition, it was shown that theanine bound to AMPA receptors not to NMDA receptors (Kakuda et al 2002a). Thus, we supposed AMPA receptors to be involved in the effects of theanine on glycine levels in the perfusate.…”

“…1). Therefore, the purpose of many recent studies on theanine was to determine whether the effects of theanine are related to its metabolism to glutamic acid (Sugiyama and Sadzuka 2003;Kakuda et al 2002a;Tsuge et al 2003). Using an in vivo brain microdialysis method, we showed that direct administration of theanine into the rat brain striatum enhanced the release of dopamine (Yokogoshi et al 1998a).…”

“…Moreover, some reports suggested that the neuroprotective effect of theanine occurs via glutamate receptors, with theanine acting as a glutamate receptor antagonist (Kakuda et al 2000a;Kakuda 2002b). Some of these reports also suggested that theanine is concerned with glutamate receptors, although the affinity of theanine to glutamate receptors was low (Kakuda et al 2002a). From these results and a report that dopamine release is enhanced when glutamic acid is increased in the interstitium (Globus et al 1988;Moghaddam et al 1990), we expected that the effect of theanine would be similar to that of glutamic acid, i.e., enhancing excitatory neurotransmission or increasing glutamic acid release from neurons; however, we showed that theanine did not affect glutamic acid and aspartic acid release from neurons (Yamada et al 2005).…”