quisqualic acid


Summary: An agonist at two subsets of excitatory amino acid receptors, ionotropic receptors that directly control membrane channels and metabotropic receptors that indirectly mediate calcium mobilization from intracellular stores. The compound is obtained from the seeds and fruit of Quisqualis chinensis.

Top Publications

  1. Loureiro dos Santos N, Reis R, Kubrusly R, de Almeida O, Gardino P, de Mello M, et al. Inhibition of choline acetyltransferase by excitatory amino acids as a possible mechanism for cholinergic dysfunction in the central nervous system. J Neurochem. 2001;77:1136-44 pubmed
    ..Veratridine (3 microM) also reduced ChAT by a Ca(2+) dependent, but glutamate independent mechanism and was prevented by 1 microM tetrodotoxin. ..
  2. Fischer A, Seltner R, Poon J, Stell W. Immunocytochemical characterization of quisqualic acid- and N-methyl-D-aspartate-induced excitotoxicity in the retina of chicks. J Comp Neurol. 1998;393:1-15 pubmed
    A single, large dose of N-methyl-D-aspartate (NMDA) or quisqualic acid (QA) injected into the chick eye has been shown previously to destroy many retinal amacrine cells and to induce excessive ocular growth accompanied by myopia...
  3. Malherbe P, Kew J, Richards J, Knoflach F, Kratzeisen C, Zenner M, et al. Identification and characterization of a novel splice variant of the metabotropic glutamate receptor 5 gene in human hippocampus and cerebellum. Brain Res Mol Brain Res. 2002;109:168-78 pubmed
    ..The only major functional difference is the increased sensitivity of hmGlu5d to protein kinase C (PKC)-mediated desensitization, relative to hmGlu5a. ..
  4. Keirstead S, Miller R. Metabotropic glutamate receptor agonists evoke calcium waves in isolated Müller cells. Glia. 1997;21:194-203 pubmed
    ..The Ca2+ waves evoked in Müller cells by neurotransmitters could represent a form of signaling from the outer retinal layers to the inner ones. ..
  5. Carter A, Muller R. Activation of excitatory amino acid receptors cannot alone account for anoxia-induced impairment of protein synthesis in rat hippocampal slices. J Neurochem. 1991;57:888-96 pubmed
    ..These results indicate that the activation of excitatory amino acid receptors cannot alone account for anoxia-induced impairment of protein synthesis in rat hippocampal slices. ..
  6. Mody N, Hermans E, Nahorski S, Challiss R. Inhibition of N-linked glycosylation of the human type 1alpha metabotropic glutamate receptor by tunicamycin: effects on cell-surface receptor expression and function. Neuropharmacology. 1999;38:1485-92 pubmed
    ..Our data suggest that non-N-glycosylated human mGlu1alpha receptors can traffic to the cell surface and activate phospholipase C. ..
  7. Magnuson D, Peet M, Curry K, McLennan H. The action of quinolinate in the rat spinal cord in vitro. Can J Physiol Pharmacol. 1987;65:2483-7 pubmed
    ..These findings suggest that a fourth amino acid receptor responsible for quinolinate's action in the spinal cord may exist. ..
  8. Jiang J, Nagaraju M, Meyer R, Zhang L, Hamelberg D, Hall R, et al. Extracellular calcium modulates actions of orthosteric and allosteric ligands on metabotropic glutamate receptor 1?. J Biol Chem. 2014;289:1649-61 pubmed publisher
  9. Matute C, Miledi R. Neurotransmitter receptors and voltage-dependent Ca2+ channels encoded by mRNA from the adult corpus callosum. Proc Natl Acad Sci U S A. 1993;90:3270-4 pubmed
    ..These results indicate that glial cells in the adult corpus callosum possess mRNA encoding functional neurotransmitter receptors and Ca2+ channels. These molecules may provide a mechanism for glial-neuronal interactions. ..

More Information


  1. Cai Z, McCaslin P. Acute, chronic and differential effects of several anesthetic barbiturates on glutamate receptor activation in neuronal culture. Brain Res. 1993;611:181-6 pubmed
    ..A similar hyperresponsiveness was not seen after the chronic treatment with phenobarbital.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  2. Nicodemo A, Pampillo M, Ferreira L, Dale L, Cregan T, Ribeiro F, et al. Pyk2 uncouples metabotropic glutamate receptor G protein signaling but facilitates ERK1/2 activation. Mol Brain. 2010;3:4 pubmed publisher
    ..Our data reveal that Pyk2 couples the activation mGluRs to the mitogen-activated protein kinase pathway even though it attenuates mGluR1-dependent G protein signaling. ..
  3. Hermans E, Nahorski S, Challiss R. Reversible and non-competitive antagonist profile of CPCCOEt at the human type 1alpha metabotropic glutamate receptor. Neuropharmacology. 1998;37:1645-7 pubmed
    ..76+/-0.18; n=3). This suggests that CPCCOEt antagonizes type 1alpha metabotropic glutamate receptor activation by interacting with a site distinct from the agonist binding site. ..
  4. Brodbelt A, Stoodley M, Watling A, Tu J, Jones N. Fluid flow in an animal model of post-traumatic syringomyelia. Eur Spine J. 2003;12:300-6 pubmed
    ..of post-traumatic syringomyelia was established in 25 Sprague-Dawley rats with intraparenchymal injections of quisqualic acid and kaolin-induced arachnoiditis...
  5. Bandrowski A, Ashe J, Crawford C. Tetanic stimulation and metabotropic glutamate receptor agonists modify synaptic responses and protein kinase activity in rat auditory cortex. Brain Res. 2001;894:218-32 pubmed
    ..These data suggest that group I mGluRs are involved in potentiating the f-EPSP by a PKC and possibly PKA dependent mechanism which is separate from the mechanism that decreases the f-EPSP and f-IPSP. ..
  6. Li Y, Dharkar P, Han T, Serpe M, Lee C, Mayer M. Novel Functional Properties of Drosophila CNS Glutamate Receptors. Neuron. 2016;92:1036-1048 pubmed publisher
    ..The unexpected ligand-binding profiles of insect iGluRs allows classical tools to be used in novel approaches for the study of synaptic regulation. VIDEO ABSTRACT. ..
  7. Birrell G, Marcoux F. Excitatory amino acid receptor-stimulated phosphoinositide turnover in primary cerebrocortical cultures. Br J Pharmacol. 1993;109:379-85 pubmed
    ..The partial dependence of the responses to quisqualate, ibotenate and glutamate on the presence of extracellular calcium suggests that the effects of these agonists may be mediated by more than one receptor subtype. ..
  8. Chiang A, Pszczolkowski M, Liu H, Lin S. Ionotropic glutamate receptors mediate juvenile hormone synthesis in the cockroach, Diploptera punctata. Insect Biochem Mol Biol. 2002;32:669-78 pubmed
    ..The metabotropic-subtype and ionotropic AMPA-subtype L-glutamate receptors are unlikely to be present on active CA cells. ..
  9. Addae J, Stone T. Interactions between topically applied excitatory amino acids on rat cerebral cortex: discrimination by pentobarbitone. Exp Brain Res. 1987;68:613-8 pubmed
    ..Similarly, quisqualic acid prevented the effects of NMDLA or kainic acid but not that of carbachol...
  10. Abraham K, McGinty J, Brewer K. Spinal and supraspinal changes in opioid mRNA expression are related to the onset of pain behaviors following excitotoxic spinal cord injury. Pain. 2001;90:181-90 pubmed
    ..Intraspinal injection of quisqualic acid (QUIS) produces an excitotoxic injury that leads to the onset of behavioral syndromes, believed to be related ..
  11. Thandi S, Blank J, Challiss R. Group-I metabotropic glutamate receptors, mGlu1a and mGlu5a, couple to extracellular signal-regulated kinase (ERK) activation via distinct, but overlapping, signalling pathways. J Neurochem. 2002;83:1139-53 pubmed
  12. Scandroglio P, Brusa R, Lozza G, Mancini I, Petrò R, Reggiani A, et al. Evaluation of cannabinoid receptor 2 and metabotropic glutamate receptor 1 functional responses using a cell impedance-based technology. J Biomol Screen. 2010;15:1238-47 pubmed publisher
    ..Overall, these results confirm the possibility of using cell impedance-based technology to study the pharmacological profile of ligands acting at G-protein-coupled receptors coupled to different downstream signaling pathways. ..
  13. Lombardi G, Alesiani M, Leonardi P, Cherici G, Pellicciari R, Moroni F. Pharmacological characterization of the metabotropic glutamate receptor inhibiting D-[3H]-aspartate output in rat striatum. Br J Pharmacol. 1993;110:1407-12 pubmed
    ..L-CCG-I), (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) and quisqualic acid (Quis). 2-Amino-4-phosphonobutyrate (L-AP4) was inactive up to 300 microM...
  14. Malherbe P, Kratochwil N, Mühlemann A, Zenner M, Fischer C, Stahl M, et al. Comparison of the binding pockets of two chemically unrelated allosteric antagonists of the mGlu5 receptor and identification of crucial residues involved in the inverse agonism of MPEP. J Neurochem. 2006;98:601-15 pubmed
    ..48) and Phe787(6.51) are essential equally in antagonism and inverse agonism effects emphasizes again the key role of these residues and the involvement of a common transmembrane network in receptor inactivation by MPEP. ..
  15. Brauner Osborne H, Jensen A, Sheppard P, Brodin B, Krogsgaard Larsen P, O HARA P. Cloning and characterization of a human orphan family C G-protein coupled receptor GPRC5D. Biochim Biophys Acta. 2001;1518:237-48 pubmed
  16. Hedberg T, Sperber E, Veliskova J, Moshe S. Laminar and temporal heterogeneity of NMDA/metabotropic glutamate receptor binding in posterior cingulate cortex. J Neurophysiol. 2000;84:1881-7 pubmed
  17. Bermack J, Debonnel G. Distinct modulatory roles of sigma receptor subtypes on glutamatergic responses in the dorsal hippocampus. Synapse. 2005;55:37-44 pubmed
    ..This modulatory role has implications for disorders that involve glutamatergic transmission in the hippocampus. ..
  18. Sacaan A, Santori E, Rao T. (S)-4-carboxy-3-hydroxyphenylglycine activates phosphatidyl inositol linked metabotropic glutamate receptors in different brain regions of the neonatal rat. Neurochem Int. 1998;32:77-85 pubmed
    ..The rank order of potency of agonists in the PI hydrolysis assay was identical in all brain regions: quisqualic acid (Quis) > (RS)-3,5-dihydroxyphenylglycine (3,5-DHPG) > 1S, 3R-aminocyclopentane dicarboxylic acid (1S,3R-..
  19. Møllerud S, Kastrup J, Pickering D. A pharmacological profile of the high-affinity GluK5 kainate receptor. Eur J Pharmacol. 2016;788:315-320 pubmed publisher
    ..The distinct pharmacological profile of GluK5 suggests that it would be possible to design ligands with selectivity towards GluK5. ..
  20. Hintermann S, Vranesic I, Allgeier H, Brülisauer A, Hoyer D, Lemaire M, et al. ABP688, a novel selective and high affinity ligand for the labeling of mGlu5 receptors: identification, in vitro pharmacology, pharmacokinetic and biodistribution studies. Bioorg Med Chem. 2007;15:903-14 pubmed
  21. Street V, Bosma M, Demas V, Regan M, Lin D, Robinson L, et al. The type 1 inositol 1,4,5-trisphosphate receptor gene is altered in the opisthotonos mouse. J Neurosci. 1997;17:635-45 pubmed
    ..These data suggest that the convulsions and ataxia observed in opt mice may be caused by the physiological dysregulation of a functional IP3R1 protein. ..
  22. Hermans E, Saunders R, Selkirk J, Mistry R, Nahorski S, Challiss R. Complex involvement of pertussis toxin-sensitive G proteins in the regulation of type 1alpha metabotropic glutamate receptor signaling in baby hamster kidney cells. Mol Pharmacol. 2000;58:352-60 pubmed
    ..The latter are involved in the negative control of phospholipase C activity while also influencing the rate of desensitization of the mGlu1alpha receptor. ..
  23. Li Volsi G, Licata F, Fretto G, Mauro M, Santangelo F. Influence of serotonin on the glutamate-induced excitations of secondary vestibular neurons in the rat. Exp Neurol. 2001;172:446-59 pubmed
    ..A minor involvement of other 5-HT receptors (at least 5-HT(1A)) and other glutamate receptors (for quisqualate and kainate) in the modulatory action of 5-HT is plausible. ..
  24. Collin T, Franconville R, Ehrlich B, Llano I. Activation of metabotropic glutamate receptors induces periodic burst firing and concomitant cytosolic Ca2+ oscillations in cerebellar interneurons. J Neurosci. 2009;29:9281-91 pubmed publisher
    ..The slow, highly regular oscillations observed in the present work are likely to drive pauses in postsynaptic Purkinje cells, and could play a role in coordinating slow oscillations involving the cerebello-olivar circuit loop. ..
  25. Shibata O, Tanaka J, Nomura M. Non-NMDA glutamatergic receptors modulate acetylcholine release in the rat subfornical organ area. Auton Neurosci. 2006;124:96-102 pubmed
    ..Perfusion of either non-N-methyl-d-aspartate (NMDA) agonist quisqualic acid (QA, 50 microM) or kainic acid (KA, 50 microM) through the microdialysis probe significantly enhanced the ACh ..
  26. Guidetti P, Amori L, Sapko M, Okuno E, Schwarcz R. Mitochondrial aspartate aminotransferase: a third kynurenate-producing enzyme in the mammalian brain. J Neurochem. 2007;102:103-11 pubmed
    ..KAT II was most abundant in rat and human brain, while mitAAT played the major role in mouse brain. It remains to be seen if mitAAT participates in cerebral KYNA synthesis under physiological and/or pathological conditions in vivo. ..
  27. Bailey A, Lee J. Lesions to the nucleus basalis magnocellularis lower performance but do not block the retention of a previously acquired learning set. Brain Res. 2007;1136:110-21 pubmed
    ..of ODLS, animals were lesioned bilaterally in the nucleus basalis magnocellularis (nBM) using either quisqualic acid (QUIS) or 192 IgG-saporin (SAP)...
  28. Adesanya A, Held D, Liu N. Geranium intoxication induces detoxification enzymes in the Japanese beetle, Popillia japonica Newman. Pestic Biochem Physiol. 2017;143:1-7 pubmed publisher
    ..on the petals of one of its preferred host plant, Pelargonium×hortorum, or on artificial diet containing quisqualic acid (QA), the active compound in zonal geranium...
  29. Blue M, Martin L, Brennan E, Johnston M. Ontogeny of non-NMDA glutamate receptors in rat barrel field cortex: I. Metabotropic receptors. J Comp Neurol. 1997;386:16-28 pubmed
    ..We conclude from the developmental localization of mGluRs that the spatiotemporal regulated expression of these receptors may influence barrel maturation and plasticity. ..
  30. Prosperi C, Scali C, Pepeu G, Casamenti F. NO-flurbiprofen attenuates excitotoxin-induced brain inflammation, and releases nitric oxide in the brain. Jpn J Pharmacol. 2001;86:230-5 pubmed
    ..We investigated, in vivo, the effects of NO-flurbiprofen on brain inflammation in rats injected with quisqualic acid into the nucleus basalis and on the release of nitric oxide from the drug in naive rat brains...
  31. Lisy V, Stastny F. Nitric oxide synthase inhibition and glutamate binding in quinolinate-lesioned rat hippocampus. Physiol Res. 2002;51:299-307 pubmed
    ..Therefore, the additional mechanisms of QUIN action, different from direct NMDA receptor activation/NO production (e.g. lipid peroxidation induced by QUIN-Fe-complexes) cannot be excluded. ..
  32. Koyama Y, Baba A, Iwata H. L-[35S]cysteic acid selectively detects chloride-dependent L-glutamate transporters in synaptic membrane. Brain Res. 1989;487:113-9 pubmed
    ..These results show that L-[35S]CA selectively detects the Cl- -dependent L-Glu transporters in synaptic membrane. ..
  33. Mesters J, Henning K, Hilgenfeld R. Human glutamate carboxypeptidase II inhibition: structures of GCPII in complex with two potent inhibitors, quisqualate and 2-PMPA. Acta Crystallogr D Biol Crystallogr. 2007;63:508-13 pubmed
    ..The common denominator for high-affinity binding to the S1' site is the formation of two strong salt bridges. ..
  34. Yamada K, Rothman S. Diazoxide blocks glutamate desensitization and prolongs excitatory postsynaptic currents in rat hippocampal neurons. J Physiol. 1992;458:409-23 pubmed
    ..DZ and perhaps related compounds will ultimately help us identify the regions of the AMPA/KA receptor responsible for desensitization. ..
  35. Speyer C, Smith J, Banda M, Devries J, Mekani T, Gorski D. Metabotropic glutamate receptor-1: a potential therapeutic target for the treatment of breast cancer. Breast Cancer Res Treat. 2012;132:565-73 pubmed publisher
    ..Even more promising, Riluzole, because it is an oral drug that can be administered with low toxicity, represents a promising approach in the treatment of triple negative breast cancer. ..
  36. Chase L, Peterson N, Koerner J. The lathyrus toxin, beta-N-oxalyl-L-alpha,beta-diaminopropionic acid (ODAP), and homocysteic acid sensitize CA1 pyramidal neurons to cystine and L-2-amino-6-phosphonohexanoic acid. Toxicol Appl Pharmacol. 2007;219:1-9 pubmed
    A brief exposure of hippocampal slices to L-quisqualic acid (QUIS) sensitizes CA1 pyramidal neurons 30- to 250-fold to depolarization by certain excitatory amino acids analogues, e.g...
  37. Urazaev A, Grossfeld R, Fletcher P, Speno H, Gafurov B, Buttram J, et al. Synthesis and release of N-acetylaspartylglutamate (NAAG) by crayfish nerve fibers: implications for axon-glia signaling. Neuroscience. 2001;106:237-47 pubmed
  38. Jin R, Horning M, Mayer M, Gouaux E. Mechanism of activation and selectivity in a ligand-gated ion channel: structural and functional studies of GluR2 and quisqualate. Biochemistry. 2002;41:15635-43 pubmed
    ..The hydrophobic pocket, which is predicted to vary in chemical character between receptor subtypes, probably plays an important role in determining receptor subtype specificity. ..
  39. Mayer M. Crystal structures of the GluR5 and GluR6 ligand binding cores: molecular mechanisms underlying kainate receptor selectivity. Neuron. 2005;45:539-52 pubmed
    ..This, together with extensive interdomain contacts between domains 1 and 2 of GluR5 and GluR6, absent from AMPA receptors, likely contributes to the high stability of GluR5 and GluR6 kainate complexes. ..
  40. Brewer K, Nolan T. Spinal and supraspinal changes in tumor necrosis factor-alpha expression following excitotoxic spinal cord injury. J Mol Neurosci. 2007;31:13-21 pubmed
    ..Mice received intraspinal injections of quisqualic acid (QUIS) to create an excitotoxic injury that is known to result in pain behaviors...
  41. Ruzicka B, Jhamandas K. Elevation of Met-enkephalin-like immunoreactivity in the rat striatum and globus pallidus following the focal injection of excitotoxins. Brain Res. 1990;536:227-39 pubmed
    ..r. levels do not appear to correspond to the enkephalin deficit seen in HD, such a deficit may be discernible in different parameters of enkephalinergic cell function.(ABSTRACT TRUNCATED AT 400 WORDS) ..
  42. Bareiss S, Dugan E, Brewer K. PI3K mediated activation of GSK-3β reduces at-level primary afferent growth responses associated with excitotoxic spinal cord injury dysesthesias. Mol Pain. 2015;11:35 pubmed publisher
    ..Excitotoxic SCI using intraspinal quisqualic acid (QUIS) resulted in inhibition of GSK-3β in the superficial spinal cord dorsal horn and adjacent DRG...
  43. Fischer A, Miethke P, Morgan I, Stell W. Cholinergic amacrine cells are not required for the progression and atropine-mediated suppression of form-deprivation myopia. Brain Res. 1998;794:48-60 pubmed
    ..by intraocular injections of either ethylcholine mustard aziridinium ion (ECMA; a selective cholinotoxin) or quisqualic acid (QA; an excitotoxin that destroys many amacrine cells, including those that release acetylcholine)...
  44. Hermit M, Greenwood J, Brauner Osborne H. Mutation-induced quisqualic acid and ibotenic acid affinity at the metabotropic glutamate receptor subtype 4: ligand selectivity results from a synergy of several amino acid residues. J Biol Chem. 2004;279:34811-7 pubmed
    ..Our approach has been to increase the affinity of the classic mGluR1 agonists, quisqualic acid and ibotenic acid, at mGluR4 by making various point mutations that mimicked mGluR1 residues...
  45. Cappuccio I, Spinsanti P, Porcellini A, Desiderati F, De Vita T, Storto M, et al. Endogenous activation of mGlu5 metabotropic glutamate receptors supports self-renewal of cultured mouse embryonic stem cells. Neuropharmacology. 2005;49 Suppl 1:196-205 pubmed
    ..These data support a critical role for mGlu receptors in early development showing that mGlu5 receptors are expressed by ES cells and their activation sustains ES cell self-renewal in culture. ..
  46. Gigler G, Móricz K, Agoston M, Simo A, Albert M, Benedek A, et al. Neuroprotective and anticonvulsant effects of EGIS-8332, a non-competitive AMPA receptor antagonist, in a range of animal models. Br J Pharmacol. 2007;152:151-60 pubmed
    ..EGIS-8332 seems suitable for further development for the treatment of epilepsy, ischaemia and stroke based on its efficacy in a variety of experimental disease models, and on its low side effect potential. ..
  47. Tu J, Liao J, Stoodley M, Cunningham A. Reaction of endogenous progenitor cells in a rat model of posttraumatic syringomyelia. J Neurosurg Spine. 2011;14:573-82 pubmed publisher
    ..5 ?l of a 24-mg/ml quisqualic acid spinal cord injection at the C-8 level to mimic an excitotoxic injury with an initial cyst, and 10 ?l of a ..
  48. Selkirk J, Naeve G, Foster A. Blockade of excitatory amino acid transporters in the rat hippocampus results in enhanced activation of group I and group III metabotropic glutamate receptors. Neuropharmacology. 2003;45:885-94 pubmed
    ..These results provide evidence of a role for EAATs in the regulation of mGluR5 and group III mGluRs in the rat hippocampus, which may have therapeutic implications. ..
  49. Malherbe P, Kratochwil N, Zenner M, Piussi J, Diener C, Kratzeisen C, et al. Mutational analysis and molecular modeling of the binding pocket of the metabotropic glutamate 5 receptor negative modulator 2-methyl-6-(phenylethynyl)-pyridine. Mol Pharmacol. 2003;64:823-32 pubmed
  50. Levi R, Selverston A. Mechanisms underlying type I mGluR-induced activation of lobster gastric mill neurons. J Neurophysiol. 2006;96:3378-88 pubmed
  51. Dalfo E, Albasanz J, Martin M, Ferrer I. Abnormal metabotropic glutamate receptor expression and signaling in the cerebral cortex in diffuse Lewy body disease is associated with irregular alpha-synuclein/phospholipase C (PLCbeta1) interactions. Brain Pathol. 2004;14:388-98 pubmed
    ..Finally, these results emphasize the emergence of a functional neuropathology that has to be explored for a better understanding of the effects of abnormal protein interactions in degenerative diseases of the nervous system. ..
  52. Tharmalingam S, Burns A, Roy P, Hampson D. Orthosteric and allosteric drug binding sites in the Caenorhabditis elegans mgl-2 metabotropic glutamate receptor. Neuropharmacology. 2012;63:667-74 pubmed publisher
  53. Keinanen K, Wisden W, Sommer B, Werner P, Herb A, Verdoorn T, et al. A family of AMPA-selective glutamate receptors. Science. 1990;249:556-60 pubmed