GABA transamination regulates neuronal glutamate content in the retina

We have used quantitative immunocytochemistry to examine the content of GABA and glutamate in rabbit retinae where the enzyme GABA transaminase has been selectively inhibited. Inhibition of GABA breakdown led not only to the expected rise in GABA levels in neurones and glial cells but also to a reduction in neuronal pools of glutamate, particularly in neuronal elements in the inner plexiform layer. We suggest that a significant proportion of the glutamate pool in nerve terminals is derived from GABA via the GABA shunt. This observation is of practical significance since GABA transaminase inhibitors are used in the treatment of epilepsy; accordingly GABA-transaminase inhibitors may modify uncontrolled excitatory episodes in the brain both by raising levels of GABA, and reducing levels of the excitatory transmitter, glutamate.