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In pharmacology, GABA A receptor positive allosteric modulators, also known as GABAkines or GABA A receptor potentiators, [1] are positive allosteric modulator (PAM) molecules that increase the activity of the GABA A receptor protein in the vertebrate central nervous system. GABA is a major inhibitory neurotransmitter in the central nervous system.
The ionotropic GABA A receptor protein complex is also the molecular target of the benzodiazepine class of tranquilizer drugs. Benzodiazepines do not bind to the same receptor site on the protein complex as does the endogenous ligand GABA (whose binding site is located between α- and β-subunits), but bind to distinct benzodiazepine binding sites situated at the interface between the α- and ...
[39] [40] However, since GABA С receptors are closely related in sequence, structure, and function to GABA A receptors and since other GABA A receptors besides those containing ρ subunits appear to exhibit GABA С pharmacology, the Nomenclature Committee of the IUPHAR has recommended that the GABA С term no longer be used and these ρ ...
The glutamate/GABA–glutamine cycle is a metabolic pathway that describes the release of either glutamate or GABA from neurons which is then taken up into astrocytes (non-neuronal glial cells). In return, astrocytes release glutamine to be taken up into neurons for use as a precursor to the synthesis of either glutamate or GABA. [2]
It also has low micromolecular affinity to GABA with a Michaelis-Menten constant of 2.5 μM, [1] and requires the presence of Cl- ions in the extracellular matrix. The GABA transporter help creates an equilibrium of GABA and will work in the reverse direction if needed to maintain the baseline concentration of GABA in the system. [1]
The GABAA beta-2 subunit is a protein that in humans is encoded by the GABRB2 gene.It combines with other subunits to form the ionotropic GABAA receptors. GABA (γ-aminobutyric acid) system is the major inhibitory system in the brain, and its dominant GABAA receptor subtype is composed of α1, β2, and γ2 subunits with the stoichiometry of 2:2:1, which accounts for 43% of all GABAA receptors.
There is evidence to suggest that GABA transporters are linked to epilepsy, affective disorders, and schizophrenia. But considering that GAT1 and GAT3 are expressed at far higher levels in brain tissue, it is likely that inhibition of these transporters will have a far greater anticonvulsant effect than inhibition of GAT2 [ 2 ] and BGT1.
The stoichiometry for GABA Transporter 1 is 2 Na +: 1 Cl −: 1 GABA. [13] The presence of a Cl − /Cl − exchange is also proposed because the Cl − transported across the membrane does not affect the net charge. [14] GABA is also the primary inhibitory neurotransmitter in the cerebral cortex and has the highest level of expression within ...