Questions about GABA.

Christopher A Baker cabaker at minerva.cis.yale.edu
Sat Oct 1 12:34:37 EST 1994


Gaumond Pierre (gaumondp at ERE.UMontreal.CA) wrote:

: I heard about a substance called GABA (gamma amino butyric acid). It is said
: that this substance is a natural transmitter inhibitor. It is also sold by some
: laboratories as an anti-anxiety drug.

My perspective:
GABA is an amino acid neurotransmitter whose synthesis is derived from an 
offshoot of the Kreb's cycle of normal metabolism (the offshoot is called 
the GABA shunt).  The final step in its synthesis is the conversion of 
the acid glutamate (which is also a neurotransmitter) to GABA by the 
enzyme glutamic acid decarboxylase (GAD).  

: According to my informatins, it reduces electric activity in the brain.

I believe the primary effect of endogenous GABA is that it binds to GABA 
receptors, which generally are ion channels in neuron membranes that are 
permeable to chloride ions.  By increasing the cell's permeability to the 
negatively charged chloride ions, GABA binding indirectly opposes the 
actions of positively charged ions entering the cell.  The net effect is 
that it becomes more difficult to excite the cell that GABA has bound 
to.  

The GABA receptor also has binding sites for barbituates and 
benzodiazapines; the binding of these drugs to these areas is the primary 
source of their inhibitory (i.e., sedative) effects.  I believe that 
these drugs (e.g., Valium), when bound to the GABA receptor, enhance the 
inhibitory effects of endogenous GABA.  

I'm sure that there is a lot of information on GABA that more qualified 
people out there can give you.  Cells that release GABA are dispersed 
throughout the brain and serve a multitude of functions.  Often, GABA 
cells can be responsible for providing negative feedback in the brain 
that is necessary for proper neural function.  Investigations are already 
suggesting that the loss of GABA neurons in the cerebral cortex could 
play a role in the development of psychotic disorders such as 
schizophrenia.  

: Are there specific foods or types of diets that will increase GABA synthesis?

: Is it desirable that someone having anxiety takes GABA instead of anti-anxiety
: drugs (such as Xanax)?

I'll leave questions like these to a more qualified individual to 
answer.  I am unaware of any diet method that would increase normal GABA 
levels in the brain.  One way to affect GABA synthesis would be by 
modulating the activity or production of glutamic acid decarboxylase; we 
are currently investigating the effects of antipsychotic drugs on brain 
levels of glutamic acid decarboxylase messenger RNA (that is, the effects 
of antipsychotic drugs on the early steps of glutamic acid decarboxylase 
production).  I'm fascinated by these issues and will concede to someone 
out there who might be able to give us more insight.  :-)
--
Christopher A. Baker
Interdepartmental Neuroscience Program
Yale University School of Medicine
New Haven, CT 06510
cabaker at minerva.cis.yale.edu




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