Gamma-aminobutyric Acid In Regulation Research Articles

Diverse role of γ-aminobutyric acid in dynamic plant cell responses.

Gamma-aminobutyric acid (GABA), a four-carbon non-protein amino acid, is found in most prokaryotic and eukaryotic organisms. Although, ample research into GABA has occurred in mammals as it is a major inhibitory neurotransmitter; in plants, a role for GABA has often been suggested as a metabolite that changes under stress rather than as a signal, as no receptor or motif for GABA binding was identified until recently and many aspects of its biological function (ranging from perception to function) remain to be answered. In this review, flexible properties of GABA in regulation of plant responses to various environmental biotic and abiotic stresses and its integration in plant growth and development either as a metabolite or a signaling molecule are discussed. We have elaborated on the role of GABA in stress adaptation (i.e., salinity, hypoxia/anoxia, drought, temperature, heavy metals, plant-insect interplay and ROS-related responses) and its contribution in non-stress-related biological pathways (i.e., involvement in plant-microbe interaction, contribution to the carbon and nitrogen metabolism and governing of signal transduction pathways). This review aims to represent the multifunctional contribution of GABA in various biological and physiological mechanisms under stress conditions; the objective is to review the current state of knowledge about GABA role beyond stress-related responses. Our effort is to place findings about GABA in an organized and broader context to highlight its shared metabolic and biologic functions in plants under variable conditions. This will provide potential modes of GABA crosstalk in dynamic plant cell responses.

Gamma aminobutyric acid B and 5-hydroxy tryptamine 2A receptors functional regulation during enhanced liver cell proliferation by GABA and 5-HT chitosan nanoparticles treatment

Liver is one of the major organs in vertebrates and hepatocytes are damaged by many factors. The liver cell maintenance and multiplication after injury and treatment gained immense interest. The present study investigated the role of Gamma aminobutyric acid (GABA) and serotonin or 5-hydroxytryptamine (5-HT) coupled with chitosan nanoparticles in the functional regulation of Gamma aminobutyric acid B and 5-hydroxy tryptamine 2A receptors mediated cell signaling mechanisms, extend of DNA methylation and superoxide dismutase activity during enhanced liver cell proliferation. Liver injury was achieved by partial hepatectomy of male Wistar rats and the GABA and 5-HT chitosan nanoparticles treatments were given intraperitoneally. The experimental groups were sham operated control (C), partially hepatectomised rats with no treatment (PHNT), partially hepatectomised rats with GABA chitosan nanoparticle (GCNP), 5-HT chitosan nanoparticle (SCNP) and a combination of GABA and 5-HT chitosan nanoparticle (GSCNP) treatments. In GABA and 5-HT chitosan nanoparticle treated group there was a significant decrease (P<0.001) in the receptor expression of Gamma aminobutyric acid B and a significant increase (P<0.001) in the receptor expression of 5-hydroxy tryptamine 2A when compared to PHNT. The cyclic adenosine monophosphate content and its regulatory protein, presence of methylated DNA and superoxide dismutase activity were decreased in GCNP, SCNP and GSCNP when compared to PHNT. The Gamma aminobutyric acid B and 5-hydroxy tryptamine 2A receptors coupled signaling elements played an important role in GABA and 5-HT chitosan nanoparticles induced liver cell proliferation which has therapeutic significance in liver disease management.

Effect of sub-acute exposure to acrylamide on GABAergic neurons and astrocytes in weaning rat cerebellum

Occupational exposure and experimental intoxication of acrylamide (ACR) can produce skeletal muscle weakness and ataxia. In this study, we tested whether ACR would affect cerebellar function through the regulation of gamma-aminobutyric acid (GABA) and glial fibrillary acidic protein (GFAP) expression in cerebellum. Weaning male Sprague-Dawley rats were gavaged with ACR (5, 15, 30 mg/kg, 5 days per week) or saline for 4 weeks. Effects of ACR on the cerebellum were observed. For the 5 mg/kg group, no obvious change was observed, whereas moderate and severe ataxia were observed in the 15 mg/kg and 30 mg/kg groups, respectively. For the 15 mg/kg and 30 mg/kg groups, cerebellum concentrations of glutamate and GABA were dose-dependently decreased and increased, respectively. Moreover, the expression of GABA, the GABAergic presynaptic marker glutamate acid decarboxylase-65 (GAD65) and GFAP were significantly increased in those 2 groups. The results suggested that weaning rats were sensitive to ACR and that the toxic effects of ACR on the cerebellum may be associated with the increased expression of GABA and reactive astrocytes hypertrophy.

Ascomycin and FK506: pharmacology and therapeutic potential as anticonvulsants and neuroprotectants.

Ascomycin and FK506 are powerful calcium-dependent serine/threonine protein phosphatase (calcineurin [CaN], protein phosphatase 2B) inhibitors. Their mechanism of action involves the formation of a molecular complex with the intracellular FK506-binding protein-12 (FKBP12), thereby acquiring the ability to interact with CaN and to interfere with the dephosphorylation of various substrates. Pharmacological studies of ascomycin, FK506, and derivatives have mainly been focused on their action as immunosuppressants and therapeutic use in inflammatory skin diseases, both in animal studies and in humans. CaN inhibitors have been also proposed for the treatment of inflammatory and degenerative brain diseases. Preclinical studies suggest, however, that ascomycin and its derivatives exhibit additional pharmacological activities. Ascomycin has been shown to have anticonvulsant activity when perfused into the rat hippocampus via microdialysis probes, and ascomycin derivatives may be useful in preventing ischemic brain damage and neuronal death. Their pharmacological action in the brain may involve CaN-mediated regulation of gamma aminobutyric acid (GABA) and glutamate receptor channels, neuronal cytoskeleton and dendritic spine morphology, as well as of the inflammatory responses in glial cells. FK506 and ascomycin inhibit signaling pathways in astrocytes and change the pattern of cytokine and neurotrophin gene expression. However, brain-specific mechanisms of action other than CaN inhibition cannot be excluded. CaN is a likely potential target molecule in the treatment of central nervous system (CNS) diseases, so that the therapeutic potential of ascomycin, FK506, and nonimmunosuppressant ascomycin derivatives as CNS drugs should be further explored.

Supraspinal modulation of pain by cannabinoids: the role of GABA and glutamate

Recent physiological, pharmacological and anatomical studies provide evidence that one of the main roles of the endocannabinoid system in the brain is the regulation of gamma-aminobutyric acid (GABA) and glutamate release. This article aims to review this evidence in the context of its implications for pain. We first provide a brief overview of supraspinal regulation of nociception, followed by a review of the evidence that the brain's endocannabinoid system modulates nociception. We look in detail at regulation of supraspinal GABAergic and glutamatergic neurons by the endocannabinoid system and by exogenously administered cannabinoids. Finally, we review the evidence that cannabinoid-mediated modulation of pain involves modulation of GABAergic and glutamatergic neurotransmission in key brain regions.

GABA and picrotoxin alter expression of a maternal effect that influences pupal diapause in the flesh fly, Sarcophaga bullata

A maternal effect that operates in the flesh fly, Sarcophaga bullata Parker (Diptera: Sarcophogidae), prevents the expression of pupal diapause in the progeny of females that have been reared under short day conditions. This set of experiments tests the possibility that the maternal effect can be prevented by the use of various environmental stresses or chemical treatments administered to the mother. High and low temperature shocks, food deprivation and reducing the size of the mother were all ineffective in altering transmission of the diapause‐suppressing maternal effect. Several chemical agents, however, were effective. Gamma‐aminobutyric acid (GABA) and one of its antagonists, picrotoxin, elicited opposite responses when injected into female flies. Whereas GABA suppressed the incidence of diapause in the female’s progeny, picrotoxin increased the diapause incidence, thus suggesting the possibility of a central role for GABA in regulation of the maternal effect. Octopamine and pilocarpine injected into females also were effective in countering the maternal effect and thus permitting expression of diapause in the female’s progeny.

Phorbol esters and synthetic diacylglycerols inhibit gamma-aminobutyric acid uptake in human spermatozoa: an effect mediated by protein kinase C?

Protein kinase C (PKC) and protein kinase A (PKA) are present in human spermatozoa and probably involved in the cascade systems leading to acrosomal exocytosis. We have investigated the possibility that these two protein kinases are involved in the regulation of gamma-aminobutyric acid (GABA) uptake in human spermatozoa. Swim-up preparations of human spermatozoa were exposed to phorbol 12-myristate 13 acetate (PMA) and 1-oleoyl-2-acetyl-sn-glycerol (OAG), which are activators of PKC, and to dibutyryl cyclic AMP (dbcAMP), a PKA activator, and subsequently incubated with radiolabelled GABA. Accumulated intracellular GABA was measured in a scintillation counter. Both PMA and OAG caused inhibition of GABA uptake while dbcAMP was without effect. The inhibitory effect on GABA uptake observed following exposure to the PKC activators could, however, not be counteracted by preincubation of the sperm samples with the PKC inhibitors staurosporine or H-7. The inhibitory effect on GABA uptake following addition of PMA was enhanced by prolonged exposure to the reagent and by increased capacitation prior to addition of the reagent. A small numerical increase in the percentage of acrosome-reacted cells was observed following exposure of the sperm cells to the highest concentrations of PMA, OAG and dbcAMP. No sperm motility parameters were affected by the treatment protocols as measured using computer-assisted semen analysis (CASA).

Phospholipid-induced changes of gamma-aminobutyric acid transport in cortex grey matter in culture.

The function of membrane phospholipids (PL) in the regulation of gamma-aminobutyric acid (GABA) transport and GABA carrier binding has been investigated in organized cultures of rat cerebral cortex. The cellular lipid composition has been changed by growing the cells in a delipidated nutrient solution or by short-term exposure of the cells to PL emulsions. Introduction of PL into the cellular matrix was monitored by analysis of biologically active fluorescently labeled phosphatidylcholine (PC) or phosphatidylethanolamine (PE). Parinaroyl and dansyl derivatives were used. Conditions of maintenance as well as exogenously given PL affected the transport of GABA. Two transport systems were observed, one first-order system and one cooperative system. Saturated species of PC or PE reduced first-order GABA uptake with increase in chain length of the fatty acid residues. The effects of unsaturated PL were dependent upon the polar head. Unsaturated PC enhanced the capacity of the first-order transport of the amino acid. In comparison to cultures grown in lipid-free medium, introduction of diarachinoyl-PC into the cells increased the density of the first-order active transport sites by a factor of 8 and the affinity constant by a factor of 17. Diarachinoyl-PE reduced both kinetic parameters. GABA uptake via the cooperative system was enhanced by the unsaturated PE, not by PC. The role of endogenous PL and their asymmetric distribution was studied by application of phospholipase A2, C, and D. Stimulation of carrier activity was induced by hydrolysis of PL on the external leaflet. Inhibition occurred upon enzymatic degradation of external and cytoplasmic PL. Lipolysis also affected GABA receptor binding, suggesting that the effects observed represent the activity of both classes of binding sites, the carrier and the receptor. However the latter accounted for a small fraction of the binding. Transport of the amino acid was temperature sensitive. The temperature curve was shifted within two discontinuities, appearing in the Arrhenius plot as a function of membrane lipids. The results suggest a partitioning of the proteins between fluid and ordered lipid domains. Displacement of the protein may govern the rate constants and/or the effective protein concentration.