Study on the physiological function and application of γ—aminobutyric acid and its receptors

WANG+Zhichao

Abstract：γ-aminobutyric acid（GABA）is a functional non protein amino acid，which is widely distributed in animals and plants，in many kinds of metabolic activities，physiological activity is very high.In the animal，as an important inhibitory neurotransmitter，GABA concentration in nerve tissue，and the content in the brain tissue of about 0.1-0.6mg/ grams.With the gradual deepening of GABA research，GABA has been more and more widely used in food，animal husbandry and other industries.This paper mainly analyzes the physiological function of GABA and its receptor，and its application is also discussed for our referenc.

Keywords：γ-aminobutyric acid；γ-aminobutyric acid receptor；physiological function

1 Introduction

γ-aminobutyric acid（GABAB）is known as aminobutyric acid，which is an important inhibitory neurotransmitter.About 50% of the central synaptic site is GABA as a transmitter，to regulate the body function.There are 3 subtypes of GABA receptor，namely，GABAA receptor，GABAB receptor and GABAC receptor.GABAB receptor is a kind of metabolic receptor，GABAA receptor and GABAC receptor are ionic receptor，which plays a key role in the central nervous system and peripheral tissues，which can regulate autism，depression，epilepsy and mental disorders，such as mental disorders，and can also be used as feed additive to alleviate the harm caused by the stress response to animal husbandry.Therefore，it is very important to study GABA and its receptors.

2 Physiological characteristics of GABA and its receptors

2.1 Physiological characteristics of GABA

GABA sub type is C4H9NO2，Sub sub quality of 103.12u，which is widely distributed in animals，plants and microorganisms，the highest concentration of mammalian brain tissue，mainly distributed in the thalamus，hippocampus，basal ganglia and other regions.It can reduce the cell metabolism and the activity of neurons，reduce the influx of ions，and can promote the activity of the parasympathetic nervous system，such as compression，anti insomnia and other beneficial effects.GABA and L-glutamic acid（Lglutamic acid content in the central nervous system are in high level，L-glutamic acid main transfer nerve impulses，and GA Ba as an inhibitory neurotransmitter，mainly to prevent nerve impulse transmission.In general，they are in balance，if the imbalance，will lead to such as mental disorders and other related diseases.In addition to the distribution of GABA in the central nervous system，endocrine cells in the digestive tract and the peripheral nervous system is also widely distributed，mainly involved in feeding，digestive tract endocrine，gastrointestinal motility and other regulation.As an important neurotransmitter in the central nervous system，GABA is mainly used to achieve the function by combining with its receptor.

2.2 Physiological characteristics of GABA receptor

GABAA receptors are widely distributed in animals，and the entire nervous system and peripheral tissues are distributed.GABA activated by the GABAA receptor on the membrane of neurons to open the chloride channel，leading to the influx of chloride ions，resulting in inhibition of postsynaptic potential，to control the excitability of neurons.GABAA receptor in the lower GABA concentration，can improve the release of acetylcholine，and thus play a role in the inhibition of intestinal motility.In contrast，GABA also regulates the GABAA receptor，and BA - GA transient exposure may lead to an increase in endocytosis of GABAA receptors and downregulation of the GABAA receptor.Therefore，the inhibitory effect of GABA receptor is mediated by GABA receptor.

GABAB receptors were present in the neurons of the presynaptic and postsynaptic sites，in the mammalian neocortex and hippocampus were distribution.GABAB receptors can be divided into GABAB1 and GABAB22 species subunit.Study found that GABAB receptors in the rat pituitary subunits by steroid hormones affect the expression would appear to be differentially and decrease expression of GABAB1mRNA，andGABAB2 receptor expression increased.So，some hormone will effect of GABAB receptor expression.

GABAC receptor is a new type of GABA receptor which is a new type of chloride ion.GABAC receptor not only found in the retina，in the mammalian spinal cord，hypothalamus，pituitary and intestine were distributed，and participate in vision，memory，sleep and other functions.GABAC receptors is one of the members of the family of ligand gated ion channels，through the regulation of Cl - in membrane conductance to stabilize cell static power information and receptor channel activity，and oak bark prime of GABAC receptor channel activity will have an impact.The lower molecular weight of quercetin is the representative of flavonoids，which has a wide range of pharmacological activities.The effect of quercetin and quercetin on the activity of GABAC receptor channel was regulated by GABA，at the same time，the number of attachment in quercetin carbohydrate，play an important role in the regulation of GABAC receptor channel activity.

3 Physiological functions of GABA and its receptors

GABA is an important inhibitory neurotransmitter in the central nervous system，and it is also found in the peripheral tissues.GABA can regulate blood pressure，the treatment of epilepsy and neurological disorders and other diseases，through the hypothalamic pituitary gonadal axis to regulate hormone secretion.Therefore，GABA plays an important role in the regulation of the bodys normal physiological function.

3.1 Regulation of cognitive dysfunction

Cognition is the process of understanding and acquiring knowledge，which based on the normal function of the cerebral cortex.The study found that the level of GABA was negatively correlated with the cognitive function of auditory memory，and compared with MCI patients，the level of GABA in patients with AD is higher，therefore，GABA has a positive role in the treatment of AD patients.Some substances such as phosphorylation of synaptophysin I and cannabinoid，will lead to cognitive dysfunction through the regulation of GABA.The cannabinoid CB1 receptor repeated stimulation，can cause transmission of GABAergic lasting developmental disorders，leading to mental illness and prefrontal cortex cognitive dysfunction.At present，a new breakthrough is gained in the treatment of cognitive dysfunction，GABAB receptor antagonists can be used to treat cognitive deficits caused by cholinergic dysfunction.

3.2 Remission and treatment of disease

3.2.1 Anti inflammatory and analgesic effects

GABA has a certain effect on the treatment and regulation of disease.It is found that obesity is associated with chronic inflammation in adipose tissue，which is released by the infiltration and accumulation of macrophages to release inflammatory cytokines.Extracted from kelp 7% glutamate and 5% GABA，can inhibit the secretion of inflammatory markers，which has a positive effect on the treatment of obesity and anti inflammation.In addition，GABA has a certain therapeutic effect on analgesia.Study showed that the local release of somatostatin（SST），can conducive to the generation of excitatory trigeminal neurons by the inhibition of GABA on neurons.Therefore，the expression of SST can play an important role in the nociceptive transmission of trigeminal nerve，which can be used as a potential therapeutic target for the treatment of trigeminal neuralgia.Different types of GABA receptors play an important regulatory role in analgesia.The activity of GABAB receptors plays an important role in the pathophysiology of pain and epilepsy.If cut the level of GABAB receptor function，can lead to cerebral ischemia and neuropathic pain，however，improve the interference function of small interfering peptide at the lesion site will selectively prompted GABAB receptor function returned to normal.Therefore，the expression of GABAB receptor in the disease can be developed as a highly specific intervention treatment.

3.2.2 The role of anti epilepsy and other mental disorders

GABA can participate in the prevention and treatment of mental disorders such as epilepsy.The study found that the mutation of GABAA receptor subunit gene was associated with the onset of epilepsy，which is located in GABAA receptor gamma 2 subunit of the third transmembrane domain between intracellular loop，and a premature stop codon is produced in the Q531 protein.After gene mutation，the content of endogenous benzodiazepine related peptide is increase，to prevent the attack of epilepsy has important physiological role.GABAB receptor antagonist agents also have inhibition of convulsions，antagonist CGP46381 of the young mice anti convulsion with enhancement.This role will be accompanied by the growth of the age and decreased.Recent studies have showed that GABAB receptor mediated inhibition is controlled by inhibiting the induction of GABAA receptors to control the occurrence of epilepsy.At present，anti epileptic drugs have been synthesized by GABA derivatives.In addition，GABA on mental disorders，autism，depression and other mental disorders，there is a certain regulatory function.

3.2.3 The role of other diseases

Hypertension is an important factor leading to heart failure and other diseases，GABA can be used to assist in the treatment of hypertension and other cardiovascular diseases，It can regulate the central nervous system，and in the medulla of the vasomotor center，has a prominent suppression of the role of GABAB receptors on sympathetic nerve endings，anti blood vessel expansion of the role of GABAA receptor binding and postsynaptic，cause blood vessels to dilate，blood pressure lowering.It is found that the activation of GABA receptors is involved in the control of blood pressure and heart rhythm，which by improving the central or peripheral GABA energy system，the GABA receptor agonists and GABA receptor agonists are involved in drug therapy for cardiovascular disease.

3.3 The role of alcohol and drug addiction

Adolescent period is a key period of fine adjustment of the brain development of many neurotransmitters，alcohol and excessive intake of opioid drugs have potential harm to the development of young peoples brain，however，located in the ventral tegmental area GABAA receptor，may carry on the effective regulation.The study found that in alcohol intake after reduction in the expression of GABAA receptor α3 subunit surface，this phenomenon indicates that dopamine neurons release GABA adjusted excessive alcohol intake.If increase the level of GABA in the brain，it may improve the treatment effect of alcohol dependence.The literature research shows that as a selective non peptide NOP receptor agonist，MT-7716 can be transmitted through the mammalian central nucleus of amygdala GABA，which effectively prevents the increase of ethanol induced.In addition，the GABA receptor also modulates the effects of opioids on the body.In addition，the GABA receptor also modulates the effects of opioids on the body.Cocaine is a natural alkaloid，a small dose of cocaine to the brain cortex is excited，large doses can cause convulsions and other inhibitory effects.Baclofen is a GABAB receptor antagonist，can be used as an important drug for the treatment of cocaine addiction.The results of the study found that the treatment effect was more obvious when the large dose was used.

4 The practical application of gamma amino acid

4.1 The application of GABA in food

The production of GABA mainly includes two forms of chemical synthesis and microbial fermentation，in which the purity of GABA synthesized by the method of microbial fermentation is relatively high.The toxicity of GABA was evaluated by the synthetic process，which had no significant effect on the weight of the tissue and tissue and pathological section.Therefore，GABA can be used as the main component of a safe functional food.GABA has been widely used in food and medicine，and has become an ideal additive for organic food and green food.Research shows that GABA rich tea，against high blood pressure has a certain effect.In addition，the pumpkin，Mi Kang，tomato and other raw materials for the production of GABA containing foods，to improve the bodys immune ability and anti hypoxia ability has significant effect.

4.2 The application of GABA in animal husbandry

GABA in the domestic and foreign animal husbandry production is more widely used.In the modern breeding industry，the animals were fed with GABA，which can effectively alleviate the stress response.Heat stress can lead to the disorder of the body function，and the feeding of GABA can improve the condition，and can improve the growth performance，regulate the endocrine level and physiological function of the body.Chen Zhongs research shows that drinking distilled water for broilers with GABA，Under heat stress conditions，GABA can increase the number and weight of carcass young red blood cell，reducing respiratory rate and feed weight ratio，which showed that GABA was involved in the regulation of heat stress and improved the growth performance of the body.Tang Jia in the study，feed the chickens fed GABA solution，The organ indexes of thymus and bursa of central immune organs under heat stress were higher than those in control group，the total number of white blood cells in peripheral blood，serum lysozyme and C3 protein were increased，，so GABA can improve the production performance of chickens and promote the development of immune function.In addition to poultry，GABA also has a regulatory effect on heat stress in mammals.It was found that the rectal temperature and respiratory rate of dairy cows were decreased after heat stress in different groups were fed with different doses of GABA，and inhibit the secretion of hypothalamic pituitary adrenal axis hormones，and enhance the bodys immunity，Therefore，the feeding of GABA has a certain effect on alleviating stress.

5 Conclusion

With the gradual deepening of GABA research，the physiological function and development and utilization of GABA has become one of the hot research directions.The clinical research results show that the function of GABA and its receptor also has a significant effect on treating sleep disorders and mental retardation，anti hypertension，regulating blood sugar etc..The microbial fermentation method of GABA is one of the ideal methods for GABA synthesis，and the synthesis of GABA safety and high purity，and as a functional food additive regulation of immune function，there are many benefits to human health.As people pay more and more attention to GABA，GABA still has a lot of potential energy，So，to explore the function of GABA，to use technology，advanced means of development and utilization in different areas.Especially in the livestock industry，with the continuous development of the intensive anti disease and anti stress，GABA still has great research value and broad application prospect.

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