Γ-Aminobutyric ACID IN BRAIN: ITS FORMATION FROM GLUTAMIC ACID

Roberts, Eugene; Frankel, Sam

doi:10.1016/s0021-9258(19)50929-2

Cited by 639 publications

(73 citation statements)

References 8 publications

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“…While known as a metabolite in plants and bacteria since the beginning of the 20th century, GABA was not actively studied until its discovery as the major amine present in the brain in 1950 ( 28 , 29 ). The inhibitory function of GABA was first proposed in the late 1950s ( 30 ); however, its role remained controversial for another decade.…”

Section: Historical Perspective and Major Milestones Of Gaba B Researchmentioning

confidence: 99%

Molecular mechanisms of metabotropic GABA _B receptor function

et al. 2021

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Metabotropic γ-aminobutyric acid G protein–coupled receptors (GABAB) represent one of the two main types of inhibitory neurotransmitter receptors in the brain. These receptors act both pre- and postsynaptically by modulating the transmission of neuronal signals and are involved in a range of neurological diseases, from alcohol addiction to epilepsy. A series of recent cryo-EM studies revealed critical details of the activation mechanism of GABAB. Structures are now available for the receptor bound to ligands with different modes of action, including antagonists, agonists, and positive allosteric modulators, and captured in different conformational states from the inactive apo to the fully active state bound to a G protein. These discoveries provide comprehensive insights into the activation of the GABAB receptor, which not only broaden our understanding of its structure, pharmacology, and physiological effects but also will ultimately facilitate the discovery of new therapeutic drugs and neuromodulators.

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Section: Historical Perspective and Major Milestones Of Gaba B Researchmentioning

confidence: 99%

Molecular mechanisms of metabotropic GABA _B receptor function

et al. 2021

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“…Typically, a presynaptic neuron synthesizes and stores neurotransmitters in synaptic vesicles and, upon stimulation, releases transmitters and modulators, which diffuse across the synaptic cleft and act on receptors located on the cytoplasmic membrane of post-synaptic neurons or other target cells. Classical experiments have uncovered neurotransmitters, including acetylcholine (ACh) (Hunt and Taveau, 1906;Dale, 1914;Dale and Feldberg, 1934), noradrenaline (NA) (Oliver and Sch€ afer, 1895;Takamine, 1901Takamine, , 1902Elliot, 1904;Von Euler, 1946), histamine (Barger and Dale, 1910), 5-hydroxytryptophan (5-HT) (Erspamer and Vialli, 1937;Rapport et al, 1948), dopamine (DA) (Montagu, 1957;Carlsson et al, 1958), glutamate (Glu) (Curtis et al, 1959), and g-aminobutyric acid (GABA) (Roberts and Frankel, 1950;Udenfriend, 1950). Peptides have been discovered in the nervous system to serve as either transmitters or modulators (Von Euler and Gaddum, 1931;Hughes et al, 1975).…”

Section: Introductionmentioning

confidence: 99%

Chemoconnectomics: Mapping Chemical Transmission in Drosophila

Deng

Liu

et al. 2019

Neuron

264

243

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“…Gamma-aminobutyric acid (GABA) was first identified in 1949 as a plant metabolite [ 1 ] and, shortly after (1950), it was reported in the vertebrate brain [ 2 ]. Today, GABA has an undisputed role as the principal inhibitory neurotransmitter in the central nervous system (CNS) of vertebrates [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

GABAergic signaling by cells of the immune system: more the rule than the exception

Bhandage

Barragán

2021

Cell. Mol. Life Sci.

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Gamma-aminobutyric acid (GABA) is best known as an essential neurotransmitter in the evolved central nervous system (CNS) of vertebrates. However, GABA antedates the development of the CNS as a bioactive molecule in metabolism and stress-coupled responses of prokaryotes, invertebrates and plants. Here, we focus on the emerging findings of GABA signaling in the mammalian immune system. Recent reports show that mononuclear phagocytes and lymphocytes, for instance dendritic cells, microglia, T cells and NK cells, express a GABAergic signaling machinery. Mounting evidence shows that GABA receptor signaling impacts central immune functions, such as cell migration, cytokine secretion, immune cell activation and cytotoxic responses. Furthermore, the GABAergic signaling machinery of leukocytes is implicated in responses to microbial infection and is co-opted by protozoan parasites for colonization of the host. Peripheral GABA signaling is also implicated in inflammatory conditions and diseases, such as type 1 diabetes, rheumatoid arthritis and cancer cell metastasis. Adding to its role in neurotransmission, growing evidence shows that the non-proteinogenic amino acid GABA acts as an intercellular signaling molecule in the immune system and, as an interspecies signaling molecule in host–microbe interactions. Altogether, the data raise the assumption of conserved GABA signaling in a broad range of mammalian cells and diversification of function in the immune system.

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Γ-Aminobutyric ACID IN BRAIN: ITS FORMATION FROM GLUTAMIC ACID

Cited by 639 publications

References 8 publications

Molecular mechanisms of metabotropic GABA _B receptor function

Molecular mechanisms of metabotropic GABA _B receptor function

Chemoconnectomics: Mapping Chemical Transmission in Drosophila

GABAergic signaling by cells of the immune system: more the rule than the exception

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Γ-Aminobutyric ACID IN BRAIN: ITS FORMATION FROM GLUTAMIC ACID

Cited by 639 publications

References 8 publications

Molecular mechanisms of metabotropic GABA B receptor function

Molecular mechanisms of metabotropic GABA B receptor function

Chemoconnectomics: Mapping Chemical Transmission in Drosophila

GABAergic signaling by cells of the immune system: more the rule than the exception

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Product

Resources

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Molecular mechanisms of metabotropic GABA _B receptor function

Molecular mechanisms of metabotropic GABA _B receptor function