ENTRIES A–Z
Philip Winn in Dictionary of Biological Psychology, 2003
GABA (gamma aminobutyric acid) RECEPTORS are divided into three classes: A, B and C. The GABA-A receptor is very complex, composed of five subunits, and containing a CHLORIDE channel, estimated to be about 5 nm in diameter. There are multiple BINDING SITES on the GABA-A receptors: sites for GABA obviously exist, but there are also sites for BENZODIAZEPINE drugs, steroids, BARBITURATES and a site biding the drug PICROTOXIN. MUSCIMOL is the most frequently used AGONIST at the GABA-A receptor; BICUCULLINE LINE is the most commonly used ANTAGONIST. Bicuculline is a competitive antagonist (see COMPETITIVE- NONCOMPETITIVE BINDING); picrotoxin is a non-competitive antagonist that blocks the chloride channel. GABA-A receptors are present widely throughout the CENTRAL NERVOUS SYSTEM. GABA-B receptors, which also mediate HYPERPOLARIZATION, were discriminated from GABA-A by their insensitivity to bicuculline. The principal antagonist at these receptors is not this but BACLOFEN. GABA-B receptors appear to exist both pre- and post-synaptically and have a different distribution through the brain compared to GABA-A receptors. GABA-C receptors are less well characterized than either the A or B variants. They mediate potent inhibition when stimulated by GABA and contain a chloride channel. However, these receptors appear not to be affected by benzodiazepines, barbiturates or steroids.
Neurotransmitters in Characean Electrical Signaling
Akula Ramakrishna, Victoria V. Roshchina in Neurotransmitters in Plants, 2018
GABA is a major inhibitory neurotransmitter whose effect on Characean cells could be investigated using voltage clamp. GABA in CNS acts as a signal by regulating ion flow across cell membranes via two classes of receptors, the GABAA and GABAB (Bouché and Fromm 2004). Ionotropic GABAA receptors consist of multiple subunits that can assemble into a functional homomeric or heteromeric channel. GABA exerts its inhibitory effect in mature brain neurons by the activation of Cl− currents through GABAA receptor channels. This tends to hyperpolarize the membrane potential and inhibits excitability. In addition to acting on the ionotropic GABAA receptor, GABA is also an endogenous agonist of the GABAB receptor, which is a member of the large metabotropic G-protein coupled receptor superfamily (Lucas 2011).
Paper 5 Answers
James Day, Amy Thomson, Tamsin McAllister, Nawal Bahal in Get Through, 2014
The GABAA receptor is a ligand-gated chloride ion channel composed of five subunits (2 α, β, γ and δ) surrounding a central ion channel. GABA binds and activates the GABAA receptor, increasing the frequency of opening of the channel, increasing chloride conductance and hyperpolarizing the neuronal membrane. Benzodiazepine drugs act by binding the a-subunit of the activated receptor complex, locking the receptor in an open configuration and potentiating the affinity of GABA for the receptor. The GABAA receptor is predominantly post-synaptic throughout the CNS. The GABAA receptor is further sub-classified according to its a-subunit into BZ1 and BZ2 receptors. The BZ1 subtype is present in the spinal cord and cerebellum and is responsible for anxiolysis and anterograde amnesic effects. The BZ2 subtype is present in the spinal cord, hippocampus and cortex, with sedative and anticonvulsant effects.
GABA(A) receptor-targeted drug development -New perspectives in perioperative anesthesia
Published in Expert Opinion on Drug Discovery, 2019
Bernd Antkowiak, Gerhard Rammes
AZD-3043 (previously named THRX-918661) is a structural analog of propanidid, an agent, introduced by Bayer in 1963. In a study including 123 human subjects, AZD-3043 caused sedation and hypnosis with no pain on injection [43]. The pharmacokinetic properties were determined from bolus injections and 30-min infusions [44]. A rapid onset and fast recovery of sedation or hypnosis was observed. These findings were consistent with a high clearance and a low apparent volume of drug distribution. Clinically relevant changes in respiratory rate or arterial blood pressure were not observed and ventilation was maintained. However, these studies also reported some undesirable effects. Most important, AZD-3043 induced allergic-type reactions (erythema, chest discomfort and dyspnea) in three subjects. Another disadvantage is that the drug is formulated in a lipid, so the respective problems known from propofol emulsion possibly come into play. On the molecular level, AZD-3043 acts as a positive allosteric modulator at GABAA receptors [45]. The potency and efficacy of AZD-3043 to enhance currents through GABAA receptors expressed in Xenopus oocytes was dramatically reduced by point mutations in the β2- (β2(N289M)) and β3- (β3(N290M)) subunits of the GABAA receptor. Since similar mutations (β2(N265S and β3(N265M)) strongly attenuated the hypnotic effect of propofol in mice, it seems likely that propofol and AZD-3043 act via similar binding sites on GABAA receptors.
Moringa oleifera seed ethanol extract and its active component kaempferol potentiate pentobarbital-induced sleeping behaviours in mice via a GABAergic mechanism
Published in Pharmaceutical Biology, 2022
Wei-Liang Liu, Bai-Fen Wu, Jian-Hua Shang, Xue-Feng Wang, Yun-Li Zhao, Ai-Xiang Huang
To evaluate whether or not EEMOS and KA improved sleeping behaviours through the biosynthesis of GABA, the mice were given corresponding samples for 14 d to examine the activation of GAD65/67. Moreover, GABAA receptor subunits were also assessed. As depicted in Figure 8, compared with CG, these findings indicated that EEMOS (2 g/kg) and KA (2 mg/kg) treatment increased the expression of GAD65 and α1-subunit (p < 0.05) (Figure 8(A,C)), but did not affect the amounts of GAD67, γ2-subunits in the hypothalamus (p > 0.05; Figure 8(B,D)). Additionally, EST (2 mg/kg) significantly enhanced the amounts of GAD65 and α1-subunit (p < 0.01), but did not influence the abundance of GAD67 and γ2-subunits.
GABA and l -theanine mixture decreases sleep latency and improves NREM sleep
Published in Pharmaceutical Biology, 2019
Suhyeon Kim, Kyungae Jo, Ki-Bae Hong, Sung Hee Han, Hyung Joo Suh
GABA acts through GABA receptors. There are generally 2 types of GABA receptors: GABAA and GABAB. The most important receptor, with respect to sleep is the GABAA receptor (Gottesmann 2002). When GABA or another agonist binds to GABAA receptor, it triggers the influx of chloride ions in neuronal cells. This causes a negative membrane potential that inhibits action potential firing. In this way, GABA (and GABA-promoting compounds) reduce activity in brain cells through GABAA receptor activation. It is well-known that the activation of GABAA receptors is beneficial for sleep (Abdou et al. 2006). The structural similarity of l-theanine to the neurotransmitter glutamic acid has prompted researchers to study its potential competition binding on glutamate receptors in the nervous system (Shinozaki and Ishida 1978). l-Theanine rapidly induces changes in serotonergic and dopaminergic transmission (Yokogoshi et al. 1998). These components act as modulating receptors of the neurotransmitter GABA, which is the main inhibitory neurotransmitter in the CNS, and therefore, one of the main molecules responsible for sleeping behaviour (Zanoli and Zavatti 2008). The decreases in sleep latency, together with a slight improvement in sleep quality, are the possible reasons for the observed increase in sleep efficiency, in our study.
Related Knowledge Centers
- Bicarbonate
- Central Nervous System
- Chemical Synapse
- Chloride
- Ligand
- Membrane Potential
- Reversal Potential
- Neurotransmitter
- Ligand-Gated Ion Channel
- Γ-Aminobutyric Acid