Characterization of GABA Receptors

Enna, S.J.; McCarson, Kenneth E.

doi:10.1002/0471141755.ph0107s63

Cited by 13 publications

(6 citation statements)

References 16 publications

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“…This indicates that specific binding to GABA receptors is not the primary mechanism for the memory enhancing effects of gammapyrone in STZ rats. Nevertheless, we cannot exclude the interaction of gammapyrone with some of the 18 subunits of GABA‐A receptor, which are identified in different combinations and exert distinct effects (Enna & McCarson, ). Moreover, the binding site for GABA and benzodiazepines has been found on the same protein complex, and a large number of cavities that are capable of binding different substrates and inducing protein conformation changes exist (Sigel & Steinmann, ).…”

Section: Discussionmentioning

confidence: 99%

GABA‐containing compound gammapyrone protects against brain impairments in Alzheimer’s disease model male rats and prevents mitochondrial dysfunction in cell culture

Piļipenko

Narbute

Amara

et al. 2019

J of Neuroscience Research

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Neuroinflammation, oxidative stress, decreased glucose/energy metabolism, and disrupted neurotransmission are changes that occur early in sporadic Alzheimer’s disease (AD), manifesting as mild cognitive impairment. Recently, the imbalanced function of the gamma‐aminobutyric acid (GABA) system was identified as a critical factor in AD progression. Thus, maintaining balance among neurotransmitter systems, particularly the GABA system, can be considered a beneficial strategy to slow AD progression. The present study investigated the effects of the compound gammapyrone, a molecule containing three GABA moieties: “free” moiety attached to the position 4 of the 1,4‐dihydropyridine (DHP) ring, and two “crypto” moieties as part of the DHP scaffold. The “free” and “crypto” GABA moieties are linked by a peptide bond (–CONH–), resulting in a peptide‐mimicking structure. In a nontransgenic male rat AD model generated by intracerebroventricular (icv) streptozocin (STZ) administration, gammapyrone (0.1 and 0.5 mg/kg ip) mitigated the impairment of spatial learning and memory, prevented astroglial and microglial neuroinflammation, and normalized acetylcholine breakdown and GABA biosynthesis. In PC12 cells, gammapyrone protected against oxidative stress, mitochondrial dysfunction and apoptosis caused by the mitochondrial toxin di‐2‐ethylhexyl phthalate (DEHP). Gammapyrone did not bind to GABA‐A and GABA‐B receptors in vitro; therefore, we cannot attribute its neuroprotective action to a specific interaction with GABA receptors. Nevertheless, we suggest that the peptide‐like regulatory mechanisms of gammapyrone or its allosteric modulatory properties are essential for the observed effects. Since, the icv STZ model resembles the early stages of AD, gammapyrone, and/or its congeners could be useful in the design of anti‐dementia drugs.

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Section: Discussionmentioning

confidence: 99%

GABA‐containing compound gammapyrone protects against brain impairments in Alzheimer’s disease model male rats and prevents mitochondrial dysfunction in cell culture

Piļipenko

Narbute

Amara

et al. 2019

J of Neuroscience Research

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“…For example, different ultrastructures of GABA synapses are currently recognized, such as type 1 (primarily identified in the synaptic cleft and considered excitatory) and type 2 (generally thought to be inhibitory), which may provide distinct pharmacological sensitivity, ionic selectivity and kinetic properties (Owens and Kriegstein, 2002). Second, 18 subunits of GABA-A receptor have been identified to interact in different combinations and exert distinct effects (Enna and McCarson, 2013). Thus, compared to GABA-A receptors containing γ-subunits that are mainly localized post-synaptically, δ-subunit-containing GABA-A receptors are predominantly localized extra-synaptically.…”

Section: Discussionmentioning

confidence: 99%

Very low doses of muscimol and baclofen ameliorate cognitive deficits and regulate protein expression in the brain of a rat model of streptozocin-induced Alzheimer's disease

Piļipenko

Narbute

Beitnere

et al. 2018

European Journal of Pharmacology

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Recent studies devoted to neuroprotection have focused on the role of the gamma-aminobutyric acid (GABA) system in regulating neuroinflammatory processes which play a key role in the neurodegenerative processes observed in Alzheimer's disease (AD) by inducing glial cell overactivation and impairing neurotransmission. Data on the efficacy of classical GABA-A and GABA-B receptor agonists (muscimol and baclofen, respectively) in animal models of AD are not available. Moreover, no published studies have examined the ability of optimal doses of these compounds to prevent neuroinflammation, the alterations in neurotransmission and cognitive deficits. In the present study, we used a non-transgenic rat model of AD obtained by intracerebroventricular streptozocin (STZ) injection and assessed the effects of muscimol and baclofen at very low doses (0.01-0.05mg/kg) on spatial memory and the expression of cortical and hippocampal proteins related to neuroinflammation, namely proteins involved in astroglial functions (glial fibrillary acidic protein, GFAP), GABA synthesis (GABA synthesizing enzyme, glutamic acid decarboxylase 67, GAD67) and acetylcholine degradation (acetylcholine esterase). The presented study demonstrated that in a rat model of STZ-induced AD both muscimol and baclofen at the tested doses exerted memory-enhancing and anti-inflammatory effects, as well as normalization of acetylcholine esterase and GABA expression. We suggested that the function of very low doses of GABA receptor agonists differs from typical GABA-related inhibition and may be mediated by the allosteric sites of GABA receptors or other non-specific cell regulatory pathways.

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“…The major inhibitory neurotransmitter is GABA. GABA receptors are divided into 3 categories: GABA‐A, GABA‐B, and GABA‐Aρ (formerly known as GABA‐C) . Binding of GABA to GABA‐A receptors causes chloride influx and hyperpolarization of the cell, which inhibits future action potentials.…”

Section: Pathophysiology Of Status Epilepticusmentioning

confidence: 99%

Status epilepticus in dogs and cats, part 1: etiopathogenesis, epidemiology, and diagnosis

Golubovic

Rossmeisl

2017

J Vet Emergen Crit Care

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Characterization of GABA Receptors

Cited by 13 publications

References 16 publications

GABA‐containing compound gammapyrone protects against brain impairments in Alzheimer’s disease model male rats and prevents mitochondrial dysfunction in cell culture

GABA‐containing compound gammapyrone protects against brain impairments in Alzheimer’s disease model male rats and prevents mitochondrial dysfunction in cell culture

Very low doses of muscimol and baclofen ameliorate cognitive deficits and regulate protein expression in the brain of a rat model of streptozocin-induced Alzheimer's disease

Status epilepticus in dogs and cats, part 1: etiopathogenesis, epidemiology, and diagnosis

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