Sequence and chromosomal assignment of a human novel cDNA: similarity to gamma-aminobutyric acid transporter

2001 ◽  
Vol 79 (12) ◽  
pp. 977-984 ◽  
Author(s):  
Yuewen Gong ◽  
Manna Zhang ◽  
Li Cui ◽  
Gerald Y Minuk

Gamma-aminobutyric acid (GABA) is the predominant inhibitory neurotransmitter in the mammalian brain. Although initially thought to be confined to the central nervous system, GABAergic activity has also been described in other tissues throughout the body. In the present study, we report the cloning and localization of human GABA transporter cDNA and document its expression in various human tissues. A human liver cDNA library was initially screened by a 32P-labeled murine brain GABA transporter 3 (GAT-3) cDNA probe, and full-length cDNA was cloned by employing Marathon-Ready(tm) human kidney cDNA. The human GABA transporter cDNA encoded a 569 amino acid hydrophobic protein with 12 transmembrane domains (TMs). Search of published sequences revealed high homology with rat GAT-2, murine GAT-3 cDNA, human solute carrier family 6 member 13 (SLC6A13), and a human peripheral betaine/GABA transporter. Northern blot analyses demonstrated that the human GABA transporter is expressed strongly in the kidney and to a lesser extent in the liver and brain. The sequence was well matched with human chromosome 12p13.3, suggesting the human GABA transporter contains 14 exons. The above findings confirm the existence of and further characterize a specific GABA transporter in human tissues.Key words: sequence, chromosome, GABA, GABA transporter.

Molecules ◽  
2019 ◽  
Vol 24 (15) ◽  
pp. 2678 ◽  
Author(s):  
Dai-Hung Ngo ◽  
Thanh Sang Vo

Gamma-aminobutyric acid (Gaba) is a non-proteinogenic amino acid that is widely present in microorganisms, plants, and vertebrates. So far, Gaba is well known as a main inhibitory neurotransmitter in the central nervous system. Its physiological roles are related to the modulation of synaptic transmission, the promotion of neuronal development and relaxation, and the prevention of sleeplessness and depression. Besides, various pharmaceutical properties of Gaba on non-neuronal peripheral tissues and organs were also reported due to anti-hypertension, anti-diabetes, anti-cancer, antioxidant, anti-inflammation, anti-microbial, anti-allergy, hepato-protection, reno-protection, and intestinal protection. Therefore, Gaba may be considered as potential alternative therapeutics for prevention and treatment of various diseases. Accordingly, this updated review was mainly focused to describe the pharmaceutical properties of Gaba as well as emphasize its important role regarding human health.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Pengkai Wang ◽  
Yini Dong ◽  
Liming Zhu ◽  
Zhaodong Hao ◽  
LingFeng Hu ◽  
...  

AbstractThe aluminum (Al) cation Al3+ in acidic soil shows severe rhizotoxicity that inhibits plant growth and development. Most woody plants adapted to acidic soils have evolved specific strategies against Al3+ toxicity, but the underlying mechanism remains elusive. The four-carbon amino acid gamma-aminobutyric acid (GABA) has been well studied in mammals as an inhibitory neurotransmitter; GABA also controls many physiological responses during environmental or biotic stress. The woody plant hybrid Liriodendron (L. chinense × tulipifera) is widely cultivated in China as a horticultural tree and provides high-quality timber; studying its adaptation to high Al stress is important for harnessing its ecological and economic potential. Here, we performed quantitative iTRAQ (isobaric tags for relative and absolute quantification) to study how protein expression is altered in hybrid Liriodendron leaves subjected to Al stress. Hybrid Liriodendron shows differential accumulation of several proteins related to cell wall biosynthesis, sugar and proline metabolism, antioxidant activity, cell autophagy, protein ubiquitination degradation, and anion transport in response to Al damage. We observed that Al stress upregulated glutamate decarboxylase (GAD) and its activity, leading to increased GABA biosynthesis. Additional GABA synergistically increased Al-induced antioxidant enzyme activity to efficiently scavenge ROS, enhanced proline biosynthesis, and upregulated the expression of MATE1/2, which subsequently promoted the efflux of citrate for chelation of Al3+. We also showed similar effects of GABA on enhanced Al3+ tolerance in Arabidopsis. Thus, our findings suggest a function of GABA signaling in enhancing hybrid Liriodendron tolerance to Al stress through promoting organic acid transport and sustaining the cellular redox and osmotic balance.


Crustaceana ◽  
2020 ◽  
Vol 93 (9-10) ◽  
pp. 1123-1134
Author(s):  
Kanjana Khornchatri ◽  
Jirawat Saetan ◽  
Sirirak Mukem ◽  
Prasert Sobhon ◽  
Tipsuda Thongbuakaew

Abstract Gamma-aminobutyric acid (GABA) is a neurotransmitter that is widely spread in vertebrate and invertebrate nervous systems and modulates essential physiological roles. Previous studies have reported the distribution of several neurotransmitters throughout the central nervous system (CNS) of decapod crustaceans. However, the existence and distribution of GABA in the mud crab’s, Scylla olivacea, CNS has still not been reported. In this study, we investigated the distribution of GABA using immunohistochemistry. The result revealed that GABA immunoreactivity (-ir) was observed in neurons and fibres throughout the CNS, including the eyestalk, brain, and ventral nerve cord of S. olivacea. Therefore, the existence and extensive distribution pattern of GABA in the CNS of the male mud crab suggest its possible roles in feeding, locomotion, and also reproduction.


2020 ◽  
Vol 21 (10) ◽  
pp. 3701 ◽  
Author(s):  
Maëlle Dade ◽  
Giulia Berzero ◽  
Cristina Izquierdo ◽  
Marine Giry ◽  
Marion Benazra ◽  
...  

Glutamic acid decarboxylase (GAD) is an intracellular enzyme whose physiologic function is the decarboxylation of glutamate to gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter within the central nervous system. GAD antibodies (Ab) have been associated with multiple neurological syndromes, including stiff-person syndrome, cerebellar ataxia, and limbic encephalitis, which are all considered to result from reduced GABAergic transmission. The pathogenic role of GAD Ab is still debated, and some evidence suggests that GAD autoimmunity might primarily be cell-mediated. Diagnosis relies on the detection of high titers of GAD Ab in serum and/or in the detection of GAD Ab in the cerebrospinal fluid. Due to the relative rarity of these syndromes, treatment schemes and predictors of response are poorly defined, highlighting the unmet need for multicentric prospective trials in this population. Here, we reviewed the main clinical characteristics of neurological syndromes associated with GAD Ab, focusing on pathophysiologic mechanisms.


1994 ◽  
Vol 40 (2) ◽  
pp. 296-302 ◽  
Author(s):  
F Petty

Abstract gamma-Aminobutyric acid (GABA), an inhibitory neurotransmitter that serves about one-third of brain neurons, is involved in the development of depression and in the treatment of depression and mania with pharmacological therapy. Brain activity of GABA may be conveniently measured in plasma, and changes in plasma concentrations of GABA reflect brain GABA activity. Plasma concentrations of GABA are significantly lower than control values in about one-third of patients with major depressive disorder; concentrations are also low in patients with mania and in bipolar patients who are depressed. These low concentrations of GABA appear to persist after recovery from depression and are not increased by treatments that improve depressive symptoms. Follow-up studies suggest that GABA concentrations remain relatively constant over at least 4 years. Additionally, preliminary data suggest that low plasma GABA is a familial marker of mood disorders in a subset of patients. Despite the difficulty of demonstrating that a particular biochemical measure is a true genetic trait marker for vulnerability for development of an illness, the accumulated data suggest that low plasma GABA may represent a biological marker of vulnerability for development of various mood disorders.


1985 ◽  
Vol 33 (3) ◽  
pp. 240-248 ◽  
Author(s):  
P Somogyi ◽  
A J Hodgson ◽  
I W Chubb ◽  
B Penke ◽  
A Erdei

An antiserum to gamma-aminobutyric acid (GABA) was tested for the localization of GABAergic neurons in the central nervous system using the unlabeled antibody enzyme method under pre- and postembedding conditions. GABA immunostaining was compared with glutamate decarboxylase (GAD) immunoreactivity in the cerebellar cortex and in normal and colchicine-injected neocortex and hippocampus of cat. The types, distribution, and proportion of neurons and nerve terminals stained with either sera showed good agreement in all areas. Colchicine treatment had little effect on the density of GABA-immunoreactive cells but increased the number of GAD-positive cells to the level of GABA-positive neurons in normal tissue. GABA immunoreactivity was abolished by solid phase adsorption to GABA and it was attenuated by adsorption to beta-alanine or gamma-amino-beta-hydroxybutyric acid, but without selective loss of immunostaining. Reactivity was not affected by adsorption to glutamate, aspartate, taurine, glycine, cholecystokinin, or bovine serum albumin. The concentration (0.05-2.5%) of glutaraldehyde in the fixative was not critical. The antiserum allows the demonstration of immunoreactive GABA in neurons containing other neuroactive substances; cholecystokinin and GABA immunoreactivities have been shown in the same neurons of the hippocampus. In conclusion, antisera to GABA are good markers for the localization of GABAergic neuronal circuits.


2019 ◽  
Author(s):  
Jordan D. Chamberlain ◽  
Holly Gagnon ◽  
Poortata Lalwani ◽  
Kaitlin E. Cassady ◽  
Molly Simmonite ◽  
...  

AbstractAge-related neural dedifferentiation – reduced distinctiveness of neural representations in the aging brain– has been associated with age-related declines in cognitive abilities. But why does neural distinctiveness decline with age? Based on prior work in non-human primates, we hypothesized that the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) declines with age and is associated with neural dedifferentiation. To test this hypothesis, we used magnetic resonance spectroscopy (MRS) to measure GABA and functional MRI (fMRI) to measure neural distinctiveness in the ventral visual cortex in a set of older and younger participants. Relative to younger adults, older adults exhibited lower GABA levels and less distinct activation patterns for faces and houses in the ventral visual cortex. Furthermore, individual differences in GABA within older adults predicted individual differences in neural distinctiveness even after controlling for gray matter volume and age. These results provide novel support for the view that age-related reductions of GABA contribute to age-related reductions in neural distinctiveness (i.e., neural dedifferentiation) in the human ventral visual cortex.Significance StatementNeural representations in the ventral visual cortex are less distinguishable in older compared to younger humans, and this neural dedifferentiation is associated with age-related cognitive deficits. Animal models suggest that reductions in the inhibitory neurotransmitter gamma aminobutyric acid (GABA) may play a role. To investigate this hypothesis, we combined functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) in a study of the human ventral visual cortex. We observed reduced distinctiveness of neural patterns and reduced GABA levels in older compared to younger adults. Furthermore, older adults with higher GABA levels tended to have more distinctive neural representations. These findings suggest that reduced GABA levels contribute to age-related declines in neural distinctiveness in the human ventral visual cortex.


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