Graham Johnston

By Tina Hinton, Jane R. Hanrahan and Graham A.R. Johnston

Flavonoids, both naturally occurring and synthetic, are known to have multiple effects on the activation of ionotropic receptors for γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in our brains. They can act as positive or negative allosteric modulators, enhancing or reducing the effect of GABA. They can elicit a direct activation of the receptors. They can also act to modulate the action of other modulators. This ability to influence function via their actions on GABA receptors permits a range of effects of flavonoids, including relief of anxiety, anticonvulsant, analgesic and sedative actions.

Part of the book: Flavonoids

By Tina Hinton and Graham A. R. Johnston

Agents that antagonize the action of GABA on ionotropic receptors are widely used to probe the function of this neurotransmitter. Three such agents are in common use: bicuculline, gabazine, and picrotoxinin. These three agents produce convulsions on systemic administration but act in significantly different ways. Bicuculline is a competitive antagonist of GABAA receptors. Gabazine is also a competitive antagonist of GABAA receptors, interacting with different residues on the receptors. Picrotoxinin is a noncompetitive antagonist acting on the chloride channel of GABAA and several other ionotropic CYS-loop receptors including glycine, GABAC, and 5-HT3 receptors. Many other structurally diverse agents are now known to act as GABA receptor antagonists, providing opportunities for the discovery of agents with selectivity for the myriad of ionotropic GABA receptors. TPMPA is a selective antagonist for GABAC receptors, which are insensitive to bicuculline. Like TPMPA, many antagonists of ionotropic GABA receptors are not convulsants, indicating that there is still much to be learnt about GABA function in the brain from the study of such agents and their possible therapeutic uses. The most recently discovered GABAA receptor nonconvulsive antagonist is S44819, which is subtype selective for α5-containing receptors, and is arousing much interest in relation to cognition.

Part of the book: GABA And Glutamate

By Tina Hinton, Kong M. Li, Vincent Viengkhou, Sin Yoo Kam, Sandra Kindaro, Herbert F. Jelinek, Slade Matthews and Graham A.R. Johnston

We have previously shown that the consumption of GABA-enriched oolong tea is effective in reducing stress in a student cohort. However, key constituent content has not been previously investigated, especially as applied to a standard cup of tea. Further, it has not been substantiated whether it is the suggested GABA content or other constituents that lead to these observed changes in stress behaviour. Using reverse-phase HPLC, we determined the actual content of four chemicals known to influence stress in 200 mL cups of regular or GABA-enriched oolong tea brewed to manufacturer’s instructions. We found eight times as much γ-aminobutyric acid (GABA) and 1.5 times as much caffeine in GABA-enriched oolong tea as in regular oolong tea. In contrast, there was 10 times less epigallocatechin gallate (EGCG), and half as much theanine in the GABA-enriched tea. Thus, there are changes in multiple constituents in GABA-enriched oolong tea that may contribute to the biological effects we observed in students consuming these teas.

Part of the book: Recent Advances in the Health Benefits of Tea