GABA（56-12-2）

γ-Aminobutyric acid(GABA)（56-12-2）video

γ-Aminobutyric acid(GABA)（56-12-2）Specifications

History

γ-Aminobutyric acid(GABA) 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. In 1959, it was shown that at an inhibitory synapse on crayfish muscle fibers GABA acts like stimulation of the inhibitory nerve. Both inhibition by nerve stimulation and by applied GABA are blocked by picrotoxin.

What is γ-Aminobutyric acid(GABA)?

γ-Aminobutyric acid(GABA) is an endogenous neurotransmitter and GABA receptor agonist. It plays a role in regulating neuronal excitability throughout the nervous system. Gamma-aminobutyric acid (GABA), converted from the principal excitatory neurotransmitter glutamate in the brain, plays a role in regulating neuronal excitability by binding to its receptors, GABA-A and GABA-B, and thereby causing ion channel opening, hyperpolarization and eventually inhibition of neurotransmission. γ-Aminobutyric acid(GABA) involved in neuronal excitability, muscle tone, stem cell growth, brain development, and mood. It decrease incidence of anxiety and seizures.

γ-Aminobutyric acid(GABA) has a role as a signalling molecule, a human metabolite, a Saccharomyces cerevisiae metabolite and a neurotransmitter. It is a gamma-amino acid and a monocarboxylic acid. It derives from a butyric acid. It is a conjugate acid of a gamma-aminobutyrate. It is a tautomer of a gamma-aminobutyric acid zwitterion.

In humans, GABA is also directly responsible for the regulation of muscle tone. Although chemically it is an amino acid, GABA is rarely referred to as such in the scientific or medical communities, because the term “amino acid,” used without a qualifier, conventionally refers to the alpha amino acids, which GABA is not, nor is it ever incorporated into a protein. In spastic diplegia in humans, GABA absorption becomes impaired by nerves damaged from the condition’s upper motor neuron lesion, which leads to hypertonia of the muscles signaled by those nerves that can no longer absorb GABA.

The biological function of γ-Aminobutyric acid (GABA)

(1)Neuro transmitter

In vertebrates, γ-Aminobutyric acid acts at inhibitory synapses in the brain by binding to specific transmembrane receptors in the plasma membrane of both pre- and postsynaptic neuronal processes. This binding causes the opening of ion channels to allow the flow of either negatively charged chloride ions into the cell or positively charged potassium ions out of the cell. This action results in a negative change in the transmembrane potential, usually causing hyperpolarization. Two general classes of GABA receptor are known: GABAA in which the receptor is part of a ligand-gated ion channel complex, and GABAB metabotropic receptors, which are G protein-coupled receptors that open or close 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. In contrast, GABA exhibits both excitatory and inhibitory actions in insects, mediating muscle activation at synapses between nerves and muscle cells, and also the stimulation of certain glands. In mammals, some GABAergic neurons, such as chandelier cells, are also able to excite their glutamatergic counterparts.

(2)Brain development

While γ-Aminobutyric acid is an inhibitory transmitter in the mature brain, its actions were thought to be primarily excitatory in the developing brain. The gradient of chloride was reported to be reversed in immature neurons, with its reversal potential higher than the resting membrane potential of the cell; activation of a GABA-A receptor thus leads to efflux of Cl− ions from the cell (that is, a depolarizing current). The differential gradient of chloride in immature neurons was shown to be primarily due to the higher concentration of NKCC1 co-transporters relative to KCC2 co-transporters in immature cells. GABAergic interneurons mature faster in the hippocampus and the GABA signalling machinery appears earlier than glutamatergic transmission. Thus, GABA is considered the major excitatory neurotransmitter in many regions of the brain before the maturation of glutamatergic synapses.

In the developmental stages preceding the formation of synaptic contacts, GABA is synthesized by neurons and acts both as an autocrine (acting on the same cell) and paracrine (acting on nearby cells) signalling mediator.The ganglionic eminences also contribute greatly to building up the GABA ergic cortical cell population.

γ-Aminobutyric acid regulates the proliferation of neural progenitor cells the migration and differentiation the elongation of neurites and the formation of synapses.

γ-Aminobutyric acid also regulates the growth of embryonic and neural stem cells. GABA can influence the development of neural progenitor cells via brain-derived neurotrophic factor (BDNF) expression. GABA activates the GABAA receptor, causing cell cycle arrest in the S-phase, limiting growth.

(3)Beyond the nervous system

γ-Aminobutyric acid(GABA) ergic mechanisms have been demonstrated in various peripheral tissues and organs including, but not restricted to the intestine, stomach, pancreas, Fallopian tube, uterus, ovary, testis, kidney, urinary bladder, lung, and liver.

How does γ-Aminobutyric acid(GABA) work?

γ-Aminobutyric acid (GABA) probably represents the most important inhibitory transmitter of the mammalian CNS. Both types of GABAergic inhibition (pre- and postsynaptic) use the same GABAA receptor subtype, which acts by regulation of the chloride channel of the neuronal membrane. A second GABA receptor type, GABAB, that is a G protein–coupled receptor is not considered to be important in understanding the mechanism of hypnotics. Activation of a GABAA receptor by an agonist increases the inhibitory synaptic response of central neurons to GABA through hyperpolarization. Because many, if not all, central neurons receive some GABAergic input, this leads to a mechanism by which CNS activity can be depressed. For example, if the GABAergic interneurons are activated by an agonist that inhibits the monoaminergic structures of the brainstem, hypnotic activity will be observed. The specific neuronal structures in different brain regions affected by GABAA agonist continues to be better defined.

The benefits of γ-Aminobutyric acid(GABA)

People can usually take γ-Aminobutyric acid (GABA) by mouth (under the tongue) to enhance their sense of health. As an endogenous neurotransmitter in the human body, it has some potential benefits to the human body:

♦Relieve anxiety

♦Improve mood

♦Relieve symptoms of premenstrual syndrome (PMS)

♦Treatment of attention deficit hyperactivity disorder (ADHD)

♦Promote lean muscle growth

♦Improve exercise endurance

♦Fat burning

♦Stabilize blood pressure

♦Relieve pain

Can the γ-Aminobutyric acid(GABA) be used as supplements?

γ-Aminobutyric acid (GABA) is sold as a dietary supplement in many countries. It has been traditionally thought that exogenous GABA (i.e. taken as a supplement) doesn’t cross the blood-brain barrier, however data obtained from more current research indicates that it may be possible.

A number of commercial sources sell formulations of GABA for use as a dietary supplement, sometimes for sublingual administration. These sources typically claim that the supplement has a calming effect.

There are some over-the-counter supplements such as phenylated GABA itself directly, or Phenibut; and Picamilon (both Soviet cosmonaut products) – Picamilon combines niacin and phenylated GABA and crosses the blood–brain barrier as a prodrug that later hydrolyzes into GABA and niacin.

Is there any side effects of γ-Aminobutyric acid(GABA)?

Studies have shown that if γ-Aminobutyric acid(GABA) is taken orally correctly within a short period of time (up to 12 weeks), GABA will be safe.

Reference

• Boonstra E, de Kleijn R, Colzato LS, Alkemade A, Forstmann BU, Nieuwenhuis S (2015). “Neurotransmitters as food supplements: the effects of GABA on brain and behavior”. Front Psychol. 6: 1520. doi:10.3389/fpsyg.2015.01520. PMC 4594160. PMID 26500584.
• Li K, Xu E (June 2008). “The role and the mechanism of γ-aminobutyric acid during central nervous system development”. Neurosci Bull. 24 (3): 195–200. doi:10.1007/s12264-008-0109-3. PMC 5552538. PMID 18500393.
• Jelitai M, Madarasz E (2005). “The role of GABA in the early neuronal development”. GABA in Autism and Related Disorders. Int. Rev. Neurobiol. International Review of Neurobiology. 71. pp. 27–62. doi:10.1016/S0074-7742(05)71002-3. ISBN 9780123668721. PMID 16512345.
• 22Haynes, William M., ed. (2016). CRC Handbook of Chemistry and Physics (97th ed.). CRC Press. pp. 5–88. ISBN 978-1498754286.
• Rorsman P, Berggren PO, Bokvist K, Ericson H, Möhler H, Ostenson CG, Smith PA (1989). “Glucose-inhibition of glucagon secretion involves activation of GABAA-receptor chloride channels”. Nature. 341 (6239): 233–6. Bibcode:1989Natur.341..233R.

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