Effects of theanine, r-glutamylethylamide, on neurotransmitter release and its relationship with glutamic acid neurotransmission

Abstract

t Theanine, r-glutamylethylamide, is one of the major amino acid components in green tea and many researchers have compared theanine's effects with glutamic acid because the chemical structure is similar. In the previous study, we demonstrated that theanine can pass brain-blood barrier and may play as an agonist or an antagonist of some receptors. In this study, we investigated the effects of theanine on neurotransmitter release in the rat brain striatum by in vivo brain microdialysis and examined whether theanine affected glutamate transporters by comparing it with a glutamate transporter blocker, L-trans-Pyrrolidine-2,4-dicarboxylic acid (L-trans-2,4-PDC). Because we investigated whether the effects of theanine is similar to L-trans-2,4-PDC on the brain neurotransmission, we measured dopamine release and some amino acids release which are known as excitatory or inhibitory neurotransmitters from neurons by theanine or L-trans-2,4-PDC perfusion into the rat brain striatum. L-trans-2,4-PDC or theanine perfusion into the brain striatum caused dopamine release from dopaminergic neurons. In addition, L-trans-2,4-PDC perfusion increased glutamic acid, aspartic acid and, whereas theanine perfusion prevented aspartic acid release and increased glycine release. These results suggested that the mechanism of dopamine release caused by theanine is different from glutamate transporter blockers or glutamic acid. Further, L-trans-2,4-PDC cause excitatory neurotransmission, whereas theanine may inhibit excitatory neurotransmission and cause inhibitory neurotransmission via glycine receptors.

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

“…From these reports, we suggested that theanine did not stimulate glutamate neurotransmission directly. Thus, next, we supposed that theanine would block glutamate transporters and glutamic acid density would increase in the interstitium and enhance glutamic acid neurotransmission because some reports suggested that theanine affects glutamate transporters (Sazduka et al 2001); however, our results showed that theanine did not affect glutamate transporters (Yamada et al 2005). In addition, we found that theanine enhanced glycine perfusate concentrations in the previous study; therefore, we considered that theanine released inhibitory neurotransmitters.…”

“…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). In addition, other reports showed that the effects of theanine differ from those of glutamic acid; for instance, theanine decreased blood pressure in a dosedependent manner in spontaneously hypertensive rats (SHR) (Yokogoshi et al 1995), but glutamate did not exhibit antihypertensive action on SHR.…”

A Novel Catalytic Ability of γ-Glutamylcysteine Synthetase ofEscherichia coliand Its Application in Theanine Production

“…The substrate specificity of GCS was assayed as follows: The 0.2 ml reaction mixtures contained 15 mM ATP, 100 mM MgSO 4 , 5 g/l MSG, 2 or 10 g/l amines, and 100 mg/l (His) 6 -tagged GCS in 0.1 M Tris-HCl buffer (pH 8.5). The reaction was carried out at 37 C for 60 min, and was stopped by boiling at 100 C for 5 min.…”

“…1) Besides its graceful flavor, many physiological functions of it have been reported, including mind relaxation, 2) improvement in sleep disturbances, 3) suppression of blood pressure elevation, 4) anti-oxidation of LDL cholesterol, 5) modulation of neurotransmission, 6) neuroprotection, 7) anti-hypertension, 8) enhancement of antitumor activity, 9) and improved recognition. 10) In the tea plant, theanine is synthesized by theanine synthetase (EC 6.3.1.6), with Glu, ethylamine, and ATP as substrates, 11) but it is very labile, so it cannot be used in industrial theanine production.…”

Effects of Theanine, a Unique Amino Acid in Tea Leaves, on Memory in a Rat Behavioral Test

“…4) Other reports have indicated that theanine binds to glutamate receptors and mediates glutamate neurotransmission. 5,6) Glutamate is a major neurotransmitter in mammals, and the stimulus it gives is very important in learning and memory, 7,8) but, there have been few reports about the effect of theanine on behavior in instance learning and emotion. Behavior tests relating to learning and memory have been adopted in recent studies, such as the Morris water maze test and the passive avoidance test, but these tests involve various factors, such as fear and locomotor activity.…”