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'Gamma-aminobutyric acid' (usually abbreviated to 'GABA') is an inhibitory neurotransmitter found in the nervous systems of widely divergent species. It is the chief inhibitory neurotransmitter in the central nervous system and also in the retina.

Contents

Function

History

Synthesis

Pharmacology

See also

References

External links

Function

In vertebrates, GABA acts at inhibitory synapses in the brain. GABA acts by binding to specific transmembrane receptors in the plasma membrane of both pre- and postsynaptic neurons. This binding causes the opening of ion channels to allow either the flow of negatively-charged chloride ions into the cell or positively-charged potassium ions out of the cell. This will typically result in a negative change in the transmembrane potential, usually causing hyperpolarization. Three general classes of GABA receptor are known. These include GABA_A and GABA_C ionotropic receptors, which are ion channels themselves, and GABA_B metabotropic receptors, which are G protein-coupled receptors that open ion channels via intermediaries (G proteins).
Neurons that produce GABA as their output are called GABAergic neurons, and have chiefly inhibitory action at receptors in the adult vertebrate. Medium Spiny Cells are a typical example of inhibitory CNS GABAergic cells. GABA exhibits excitatory actions in insects, mediating muscle activation at synapses between nerves and muscle cells and also the stimulation of certain glands. In hippocampus and neocortex of the mammalian brain, GABA has primarily excitatory effects early in development, and is in fact the major excitatory neurotransmitter in many regions of the brain prior to the maturation of glutamate synapses - ''See'' ''developing cortex''. Whether GABA is excitatory or inhibitory depends on the direction (into or out of the cell) and magnitude of the ionic currents controlled by the GABA_A receptor. When net positive ionic current is directed into the cell, GABA is excitatory, when the net positive current is directed out of the cell, GABA is inhibitory. A developmental switch in the molecular machinery controlling the polarity of this current is responsible for the changes in the functional role of GABA between the neonatal and adult stages.
In spastic cerebral palsy in humans, GABA cannot be absorbed properly by the damaged nerve rootlets leading to certain muscles; this leads to hypertonia in those muscles.

History

Gamma-aminobutyric acid was first synthesized in 1883, and was first known only as a plant and microbe metabolic product. In 1950, however, GABA was discovered to be an integral part of the mammalian central nervous system.^[1]

Synthesis

Organisms synthesize GABA from glutamate using the enzyme L-glutamic acid decarboxylase and pyridoxal phosphate as a cofactor. It is worth noting that this involves converting the principal excitatory neurotransmitter (glutamate) into the principal inhibitory one (GABA).

Pharmacology

Drugs that act as agonists of GABA receptors (known as GABA analogues or ''GABAergic'' drugs) or increase the available amount of GABA typically have relaxing, anti-anxiety and anti-convulsive effects. Many of the substances below are known to cause short-term memory loss and retrograde amnesia.
GABA has been purported to increase the amount of the Human Growth Hormone. The results of those studies have been seldom replicated and have recently been in question since it is unknown if GABA can pass the blood-brain barrier.
Drugs that affect GABA receptors:

★ alcohol (ethanol)^[2][3][4]

★ avermectins—doramectin, selamectin, ivermectin

★ barbiturates

★ bicucullines

★ benzodiazepines

★ baclofen

★ tramadol

★ opiates

★ cannabinoids

★ carbamazepines

★ cyclopyrrolone derivatives—eszopiclone, zopiclone

★

★ fluoroquinolones

★ gabazine (SR-95531)

★ gamma-hydroxybutyrate (GHB)^[5]

★ imidazopyridines—zaleplon, zolpidem, zopiclone

★ kavalactones^[6]

★ muscimol

★ phenytoin

★ picrotoxin

★ progabide

★ propofol

★ phenibut

★ thujone—GABA antagonist

★ valproate
Drugs that affect GABA in other ways:

★ tiagabine—potentiates by inhibiting uptake into neurons and glia

★ vigabatrin—potentiates by inhibiting GABA-T, preventing GABA breakdown

★ tetanospasmin—primary toxin of tetanus bacteria, blocks release of GABA

See also

★ Spastic diplegia

References

1. The Biochemical Basis of Neuropharmacology, Roth, Robert J.; Cooper, Jack R.; Bloom, Floyd E., , , Oxford University Press, 2003,
2. Gamma-aminobutyric acid B receptor 1 mediates behavior-impairing actions of alcohol in Drosophila: adult RNA interference and pharmacological evidence, Dzitoyeva S, Dimitrijevic N, Manev H, , , Proc. Natl. Acad. Sci. U.S.A., 2003
3. Sites of alcohol and volatile anaesthetic action on GABA_A and glycine receptors, Mihic SJ, Ye Q, Wick MJ, Koltchine VV, Krasowski MD, Finn SE, Mascia MP, Valenzuela CF, Hanson KK, Greenblatt EP, Harris RA, Harrison NL, , , Nature, 1997
4. From gene to behavior and back again: new perspectives on GABA_A receptor subunit selectivity of alcohol actions, Boehm SL, Ponomarev I, Blednov YA, Harris RA, , , Adv. Pharmacol., 2006
5. Drosophila GABA_B receptors are involved in behavioral effects of gamma-hydroxybutyric acid (GHB), Dimitrijevic N, Dzitoyeva S, Satta R, Imbesi M, Yildiz S, Manev H, , , Eur. J. Pharmacol., 2005
6. Kava (Piper methysticum) back in circulation, Hunter, A, , , Australian Centre for Complementary Medicine, 2006

External links

★ The role of GABA in the pathogenesis and treatment of anxiety and other neuropsychiatric disorders