Turnover of GABA

Dopamine induces biochemical and physiological effects in the mammalian neostriatum. The occurrence of a D-l dopamine receptor (in the classification scheme of Kebabian and Caine) accounts for the ability of dopamine to enhance cyclic AMP formation. The occurrence of a D-2 dopamine receptor accounts for the ability of dopamine to inhibit cyclic AMP formation brought about by stimulation of a D-l dopamine receptor. Dopamine receptors mediate the regulation of (1) the release or turnover of acetylcholine (postsynaptic dopamine receptor) and (2) the release or turnover of dopar mine (presynaptic autoreceptor). Both receptors can be classified as D-2 dopamine receptors. Indications for the occurrence of dopamine receptors affecting the release or turnover of GABA, glutamate, serotonin and several neuropeptides are evaluated. 

A Postsynaptic Dopamine Receptor Regulating the Release or Turnover of GABA ... 

GABA after systemic injection is relatively smaller after 1 h than after 3 h (Walters et al., 1978). The method has been used to show a reduced turnover of GABA in striatum and substantia nigra after apomorphme administration (Hokfelt et al., 1976). 

Turnover of GABA by Infusion with Labeled Precursors... 

There exists a large body of literature on the turnover of GABA in brain In this review I have recommended the use of specific GABA-T inhibitors, such as 7-vinyl-GABA, gabaculine, and aminooxyacetic acid, that can be administered either systemically or intracerebrally... 

Evidence for a negative influence of GABAergic processes on 5-HT turnover and release in various brain areas has been reported in the rat (100) and cat (112). Further investigations are necessary, however, to demonstrate that the hallucinogenic action of muscimol involves a reduction in 5-HT turnover via the stimulation of GABA receptors. 

Alters norepinephrine turnover Reduced j8-adrenergic binding and activity Reverses age-related decline in o2 adrengic receptors GABA Elevation of GABA levels... 

The mechanism of action of valproate is complex and still the subject of uncertainty. The drug appears to act by enhancing GABAergic function. Thus it increases GABA release, inhibits catabolism and increases the density of GABA-B receptors in the brain. There is also evidence that it increases the sensitivity of GABA receptors to the action of the inhibitory transmitter. Other actions that may contribute to its therapeutic effects include a decrease in dopamine turnover, a decrease in the activity of the NMDA-glutamate receptors and also a decrease in the concentration of... 

The main effects of BZs occur via positive allosteric modulation. The BZs and GABA bind to separate sites on the GABAa receptor complex. When a BZ occupies the BZ receptor, GABA s ability to open the chloride channels increases. With greater opening of the chloride channel, cellular excitability decreases (Ballenger, 1995). The final result of this decreased cellular excitability is widespread because of the extensive inhibitory role of GABA in the CNS. As a result, BZs may alter the turnover of neurotransmitters such as norepinephrine and serotonin (5-hydroxytryptamine [5-HT]). 

Enna S. J (1981) GABA receptor pharmacology, functional considerations. Biochem Pharmacol. 30, 907-913 Felker P. (1978) Gas-hqmd chromatography of the heptafluorobutyric-O-isobutyl esters of ammo acids. J Chromatogr 153, 259-262 Fonnum F (1981) The Turnover of Transmitter Ammo Acids, With Special Reference to GABA, in Central Neurotransmitter Turnover (Pycock C J. and Tabener P V, eds.) University Press, Baltimore, pp 105-124... 

GABA is metabolized by GABA-T to succinic semialdehyde, which IS further oxidized by succinic semialdehyde dehydrogenase to succinic acid. Inhibition of GABA-T is therefore accompanied by an increase m GABA and this increase should reflect GABA turnover. The inhibition of GABA-T can be... 

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