GABAergic Effect of L-Glutamine in Rats: Potential Relevance to GH Release, Etc.

This article [Wang et al., 2007: (http://www.fasebj.org/cgi/reprint/21/4/1227)(http://www.ncbi.nlm.nih.gov/pubmed/17218538?dopt=Abstract)] shows that oral L-glutamine increases both spontaneous and stimulus-evoked (NMDA-infusion-evoked) gamma-aminobutyric acid (GABA) release in the striatum. The authors measured the tissue contents of GABA, glutamine, and glutamate and found that the oral glutamine, at either 500 mg/kg bw [this was a dose given to adult rats and roughly scales to 106 mg/kg, or a 7431-mg dose [(500/4.71) x 70], for a 70-kg human (http://hardcorephysiologyfun.blogspot.com/2008/12/equations-for-animal-food-intake-and.html)] or 2,000 mg/kg bw, increased the tissue concentrations of GABA and glutamine in the striatum but did not increase the concentration of glutamate. The measurement of the tissue concentrations of glutamine, GABA, and glutamate is a measurement of the increase in the intracellular, as opposed to extracellular, levels of those amino acids. This is because the authors measured the tissue contents at 2.5 hours post-administration, a time point at which the extracellular-fluid (ECF) GABA levels, produced in response to the glutamine-induced increases in spontaneous GABA release, would be expected to have returned to roughly baseline levels (see Figure 1A).

What they're saying is that there's a limited pool of intracellular glutamate that can be converted into GABA under baseline conditions and that glutamine does, in fact, enlarge that pool by its conversion into glutamate (by the phosphate-activated glutaminase enzymes that are expressed in both astrocytes and neurons in the brain). Their argument is valid, in my opinion, and highlights the complexity of glutamine metabolism in the brain. I found one article [Cocchi, 1976: (http://www.ncbi.nlm.nih.gov/pubmed/1020692)] describing muscle relaxant and antidepressant effects of oral glutamine at doses of 250-750 mg/d. That seems like a somewhat low dosage, but it's interesting that the author observed effects that could be construed as having been GABAergic (the "muscle relaxant" effects and supposed efficacy at very low dosages in the augmentation of antidepressant treatments). Low GABA levels have sometimes been found in people with depression [some articles on GABA in this context may show up in this search: (http://scholar.google.com/scholar?num=100&hl=en&lr=&q=GABA+antidepressant)], but one would obviously want to discuss the use of glutamine with one's doctor. This supposed GABAergic effect of glutamine may also be relevant in the context of growth hormone (GH) release, given that baclofen, a GABA-B receptor agonist, and other GABAergic drugs are known to release GH in humans. Obviously, one would want to discuss all of these issues with one's doctor before one took anything.