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- Zhang, W. et al. (2006) Biophys. J. 91, 1336.
Glutamate is the main excitatory neurotransmitter in the CNS and is also involved in a variety of pathological conditions. AMPA-type glutamate receptors are tetrameric ion channels that mediate fast excitatory synaptic transmission in the mammalian brain.
L-Quisqualic acid (Quisqualate) is a selective agonist of AMPA receptors. Quisqualate binds to the AMPA receptor subunit GluR2 at the base of a deep cleft between two globular domains (GluR2-S1S2) causing the translation and rotation of domain S2 so that the cleft closes. The rate in which quisqualate dissociates from the AMPA receptor is primarily determined by the rate at which the receptor’s binding domain opens. Mutations that destabilize the closed-cleft conformation of the receptor increase the rate of quisqualate dissociation and alter its relative efficacy1. Interestingly, although glutamate is known to cause an increase in human melanoma cell viability quisqualate does not create a similar effect even though it stimulates PI hydrolysis, thus suggesting it is a “G-protein biased agonist”2.
L-Quisqualic acid (#L-210) is a highly pure, synthetic, and biologically active compound.
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