Agonism and antagonism of γ-aminobutyric acid

Steward, E. G.; Borthwick, P. W.; Clarke, G. R.; Warner, D.

doi:10.1038/256600a0

Cited by 20 publications

(5 citation statements)

References 18 publications

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“…It is not inconceivable that bicuculline, when it binds to the GABA‐binding site, could alter the conformation of the channel. A part of the bicuculline molecule can be used to obtain an isosteric match with GABA and may account for the competitive mechanism of inhibition but the whole bicuculline structure is much larger than the size of the GABA molecule ( Steward et al ., 1975 ). It may be that the spread of charges or other structural features associated with bicuculline's larger size affect the open conformation of the receptor and thereby influence channel characteristics.…”

Section: Discussionmentioning

confidence: 99%

Bicuculline, pentobarbital and diazepam modulate spontaneous GABA_A channels in rat hippocampal neurons

Birnir

Eghbali

Everitt

et al. 2000

British J Pharmacology

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1 Spontaneously opening, chloride-selective channels that showed outward recti®cation were recorded in ripped-o patches from rat cultured hippocampal neurons and in cell-attached patches from rat hippocampal CA1 pyramidal neurons in slices. 2 In both preparations, channels had multiple conductance states and the most common singlechannel conductance varied. In the outside-out patches it ranged from 12 to 70 pS (Vp=40 mV) whereas in the cell-attached patches it ranged from 56 to 85 pS (7Vp=80 mV). 3 Application of GABA to a patch showing spontaneous channel activity evoked a rapid, synchronous activation of channels. During prolonged exposure to either 5 or 100 mM GABA, the open probability of channels decreased. Application of GABA appeared to have no immediate e ect on single-channel conductance. 4 Exposure of the patches to 100 mM bicuculline caused a gradual decrease on the single-channel conductance of the spontaneous channels. The time for complete inhibition to take place was slower in the outside-out than in the cell-attached patches. 5 Application of 100 mM pentobarbital or 1 mM diazepam caused 2 ± 4 fold increase in the maximum channel conductance of low conductance (540 pS) spontaneously active channels. 6 The observation of spontaneously opening GABA A channels in cell-attached patches on neurons in slices suggests that they may have a role in neurons in vivo and could be an important site of action for some drugs such as benzodiazepines, barbiturates and general anaesthetics.

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Section: Discussionmentioning

confidence: 99%

Bicuculline, pentobarbital and diazepam modulate spontaneous GABA_A channels in rat hippocampal neurons

Birnir

Eghbali

Everitt

et al. 2000

British J Pharmacology

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“…On spinal neurones, however, the (R)-(-)-enantiomer of 3-OH-GABA is marginally more potent than the (S) + )-enantiomer (Krogsgaard-Larsen et al, 1985), corresponding exactly to the stereoselectivity that we observed at the Ascaris GABA receptor. It has been established that the GABAA-receptor not only has rigid requirements for the structural configuration of GABAergic compounds but also the degree of delocalization of both the positive and negative charges on the molecule is a crucial determinant of GABA-mimetic activity (Steward et al, 1975). The most potent compound we have studied to date at the Ascaris muscle GABA receptor is DHM.…”

Section: )mentioning

confidence: 99%

GABA receptors on the somatic muscle cells of the parasitic nematode, Ascaris suum: stereoselectivity indicates similarity to a GABA_A‐type agonist recognition site

Holden‐Dye

Krogsgaard‐Larsen²,

Nielsen³

et al. 1989

British J Pharmacology

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1 The y-aminobutyric acid (GABA) receptors on the somatic muscle cells of Ascaris, which mediate muscle cell hyperpolarization and relaxation, have been characterized by use of intracellular recording techniques. 2 These receptors are like mammalian GABAA-receptors in that the response is mediated by an increase conductance to chloride ions. The GABAA-mimetic, muscimol, has a relative potency of 0.40 + 0.02 (n = 3) compared to GABA. 3 The stereoselectivity of the GABA receptor on Ascaris is identical to that for the mammalian GABAA-receptor, as determined from the relative potency of three pairs of enantiomers of structural analogues of GABA. 4 The most potent agonist is (S)-(+)-dihydromuscimol which is 7.53 + 0.98 (n = 5) times more potent than GABA. 5 The Ascaris GABA receptor is not significantly blocked, at concentrations below OO Mm by the potent, competitive GABAA-receptor antagonist, SR95531. 6 The Ascaris GABA receptor does not recognise agents that are known to block the GABA gated chloride channel in mammalian preparations such as t-butylbicyclophosphorothionate (TBPS, 1OpM, n = 2) or the insecticide dieldrin (100pM, n = 3). 7 GABAergic responses in Ascaris are not potentiated by pentobarbitone (100pM, n = 3) or flurazepam (100pM, n = 3). 8 The potencies of various GABA-mimetics in the Ascaris preparation have been compared with their potency at displacing GABAA-receptor binding in mammalian brain. Excluding the sulphonic acid derivatives of GABA, the correlation coefficient (r) between the potencies of compounds in the two systems is 0.74 (P < 0.01). The significance of this correlation is discussed.9 The pharmacology of the Ascaris GABA receptor is discussed in relation to other invertebrate systems and the mammalian subclassification of GABA receptors.

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“…The non-proteinogenic amino acid, GABA was reported in plants more than seven decades ago when Steward and his colleagues initially reported it as a major nitrogenous compound in the potato tubers [82]. Since this time, the physiological roles of GABA as a primary metabolite in plant growth and development, as well as stress responses have been extensively studied [44,[55][56][57][58][59][60][61].…”

Section: Discussionmentioning

confidence: 99%

Gamma-Aminobutyric Acid Supplementation Boosts the Phytohormonal Profile in ‘Candidatus Liberibacter asiaticus’-Infected Citrus

Nehela,

Killiny

2023

Plants

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The devastating citrus disease, Huanglongbing (HLB), is associated with ‘Candidatus Liberibacter sp.’ and transmitted by citrus psyllids. Unfortunately, HLB has no known sustainable cure yet. Herein, we proposed γ-aminobutyric acid (GABA) as a potential eco-friendly therapeutic solution to HLB. Herein, we used GC/MS-based targeted metabolomics combined with gene expression to investigate the role of GABA in citrus response against HLB and to better understand its relationship(s) with different phytohormones. GABA supplementation via root drench boosts the accumulation of endogenous GABA in the leaves of both healthy and ‘Ca. L. asiaticus’-infected trees. GABA accumulation benefits the activation of a multi-layered defensive system via modulating the phytohormone levels and regulating the expression of their biosynthesis genes and some pathogenesis-related proteins (PRs) in both healthy and ‘Ca. L. asiaticus’-infected plants. Moreover, our findings showed that GABA application stimulates auxin biosynthesis in ‘Ca. L. asiaticus’-infected plants via the activation of the indole-3-pyruvate (I3PA) pathway, not via the tryptamine (TAM)-dependent pathway, to enhance the growth of HLB-affected trees. Likewise, GABA accumulation was associated with the upregulation of SA biosynthesis genes, particularly the PAL-dependent route, resulting in higher SA levels that activated CsPR1, CsPR2, CsPR5, and CsWRKY70, which are prominent to activation of the SA-mediated pathway. Additionally, higher GABA levels were correlated with an enhanced JA profile and linked with both CsPR3 and CsPR4, which activates the JA-mediated pathway. Collectively, our findings suggest that exogenous GABA application might be a promising alternative and eco-friendly strategy that helps citrus trees battle HLB.

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Agonism and antagonism of γ-aminobutyric acid

Cited by 20 publications

References 18 publications

Bicuculline, pentobarbital and diazepam modulate spontaneous GABA_A channels in rat hippocampal neurons

Bicuculline, pentobarbital and diazepam modulate spontaneous GABA_A channels in rat hippocampal neurons

GABA receptors on the somatic muscle cells of the parasitic nematode, Ascaris suum: stereoselectivity indicates similarity to a GABA_A‐type agonist recognition site

Gamma-Aminobutyric Acid Supplementation Boosts the Phytohormonal Profile in ‘Candidatus Liberibacter asiaticus’-Infected Citrus

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Agonism and antagonism of γ-aminobutyric acid

Cited by 20 publications

References 18 publications

Bicuculline, pentobarbital and diazepam modulate spontaneous GABAA channels in rat hippocampal neurons

Bicuculline, pentobarbital and diazepam modulate spontaneous GABAA channels in rat hippocampal neurons

GABA receptors on the somatic muscle cells of the parasitic nematode, Ascaris suum: stereoselectivity indicates similarity to a GABAA‐type agonist recognition site

Gamma-Aminobutyric Acid Supplementation Boosts the Phytohormonal Profile in ‘Candidatus Liberibacter asiaticus’-Infected Citrus

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Bicuculline, pentobarbital and diazepam modulate spontaneous GABA_A channels in rat hippocampal neurons

Bicuculline, pentobarbital and diazepam modulate spontaneous GABA_A channels in rat hippocampal neurons

GABA receptors on the somatic muscle cells of the parasitic nematode, Ascaris suum: stereoselectivity indicates similarity to a GABA_A‐type agonist recognition site