Disease relevance of QUISQUALIC ACID

• We therefore sought to determine whether antagonists active at the NMDA or quisqualate subtypes of L-glutamate receptors prevent toxicity of either MPP+ (1-methyl-4-phenyl-pyridinium ion, the active metabolite of MPTP) or the selective dopaminergic neurotoxin 6-OHDA in the rat substantia nigra pars compacta [1].
• Using the N18-RE-105 neuroblastoma X retina cell line, we previously described Ca2(+)-dependent quisqualate-type glutamate toxicity caused by the inhibition of high-affinity cystine uptake, leading to glutathione depletion and accumulation of cellular oxidants [2].
• Finally, pertussis toxin failed to inhibit muscarinic responses, whereas it blocked greater than 70% of the quisqualate stimulation [3].
• 3. Quisqualate (QQ) and (RS)-2-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) excited many ganglion cells and were approximately as potent as KA [4].
• The first effect, observed with anoxic incubation by itself, was the diminished quisqualate (10(-5) M)-stimulated accumulation of 3H-IPs degraded from prelabeled PI under prolonged anoxia [5].

Psychiatry related information on QUISQUALIC ACID

• Quisqualate (AMPA) receptor binding was markedly reduced in the molecular layer of the cerebellum from patients with Alzheimer's disease (167 +/- 13 pmoles/gm) compared with control patients (280 +/- 13 pmoles/gm) [6].
• Preventive action of quisqualic acid against grayanotoxin-induced suppression of locomotor activity in mice [7].
• It was also effective following i.p. administration to CF#1 mice against maximal electroshock (MES)-, pentetrazole-, picrotoxin-, quisqualic acid-, and strychnine-induced seizures (ED50s: 24.9, 13.8, 43.3, 8.05, and 60.5 mg/kg, respectively) [8].
• Simple and configural association learning in rats with bilateral quisqualic acid lesions of the nucleus basalis magnocellularis [9].
• Globus pallidus and motor initiation: the bilateral effects of unilateral quisqualic acid-induced lesion on reaction times in monkeys [10].

High impact information on QUISQUALIC ACID

• We report here that certain selective NMDA antagonists (AP7, CPP, MK-801), but not the preferential quisqualate antagonists CNQX and NBQX, provided short-term (up to 24 h) protection against MPP+ toxicity when coadministered into the substantia nigra [1].
• Here we report that in mature striatal neurons in primary cultures, quisqualate can release arachidonic acid by associatively activating both quisqualate metabotropic receptors coupled to phospholipase C (Qp) and Qi receptors [11].
• The quisqualate receptor mediates the fast synaptic response evoked by low-frequency stimulation, whereas the NMDA receptor system is activated transiently by tetanic stimulation, leading to the induction of LTP [12].
• Neurobiology. Quisqualate receptor antagonists [13].
• Receptors for excitatory amino acids in the mammalian central nervous system are classified into three major subtypes, ones which prefer N-methyl-D-aspartate (NMDA), quisqualate (QA), or kainate (KA) as type agonists respectively [14].

Chemical compound and disease context of QUISQUALIC ACID

• We examined the effects of in vitro anoxia on phosphoinositide (PI) breakdown in rat hippocampal slices stimulated by glutamate and quisqualate [5].
• In an experimental model of perinatal hypoxic-ischemic brain injury, we examined quisqualic acid (Quis)-stimulated phosphoinositide (PPI) turnover in hippocampus and striatum [15].
• 6. Potassium currents induced both by quisqualate and kainate strongly depended on temperature and could be blocked by pertussis toxin [16].
• HU-211 was found to protect neurones from NMDA and quisqualate-induced toxicity but not that produced by AMPA or kainate [17].
• The neuroprotective effects of the strychnine-insensitive glycine receptor antagonist, HA-966, against N-methyl-D-aspartate (NMDA)- and quisqualate (QA)-mediated brain injury were determined in perinatal rats [18].

Biological context of QUISQUALIC ACID

• The decreased cortical binding represented a reduction in numbers of binding sites, not a change in binding affinity, and appeared to be the result of a specific decrease in numbers of the low-affinity quisqualate binding site [19].
• In the pH range between 6.6 and 8.0, changes in external [H+] had negligible influence on the amplitude and kinetics of the monovalent ion-carrying currents activated by the agonists quisqualate and kainate [20].
• Modulation of DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/quisqualate receptors by phospholipase A2: a necessary step in long-term potentiation [21]?
• In addition, kainic acid elicited a nondesensitizing inward current at short latency, and quisqualate elicited a delayed oscillatory inward current, presumably mediated by a second-messenger system [22].
• Transient transfection of this cDNA into two NAALADase-negative cell lines conferred NAAG-hydrolyzing activity that was inhibited by the NAALADase inhibitors quisqualic acid and beta-NAAG [23].

Anatomical context of QUISQUALIC ACID

• Hyperpolarization of fish retinal horizontal cells by kainate and quisqualate [24].
• Receptors for excitatory amino-acid transmitters on nerve cells fall into two main categories associated with non-selective cationic channels, the NMDA (N-methyl-D-aspartate) and non-NMDA (kainate and quisqualate) receptors [25].
• Purkinje cells responded with large inward currents accompanied by increases in dendritic [Ca2+]i when challenged with the excitatory amino acid agonists glutamate and quisqualate [26].
• This is in contrast to LTP in the hippocampus [Zalutsky, R. A. & Nicoll, R. A. (1990) Science 248, 1619-1624], where LTP is expressed by quisqualate receptors [27].
• Xenopus oocytes were used to study the interaction of neuronal quisqualate receptors with neuronal ion channels [28].

Associations of QUISQUALIC ACID with other chemical compounds

• Glutamate binds to both excitatory neurotransmitter binding sites and a Cl(-)-dependent, quisqualate- and cystine-inhibited transport site on brain neurons [29].
• Currents elicited by L-glutamate and the related agonists quisqualate and kainate were analyzed under voltage clamp in isolated goldfish horizontal cells, using the whole-cell recording configuration of the patch-clamp method [Hamill, O.P., Marty, A., Neher, E., Sakmann, B. & Sigworth, F. J. (1981) Pflügers Arch. 391, 85-100] [30].
• The results demonstrate (i) that L-glutamate binding sites may be resolved into three distinct subtypes (categories A1, A2, and A4), each corresponding to an electrophysiologically identified receptor class, and (ii) that the N-methyl aspartate (A1) and quisqualate (A2) receptor types are selectively associated with PSDs [31].
• Both stereoisomers of aspartate were effective, whereas kainate, quisqualate, N-methyl-D-aspartate, and D-glutamate were ineffective [32].
• Aniracetam is a nootropic drug that has been shown to selectively enhance quisqualate receptor-mediated responses in Xenopus oocytes injected with brain mRNA and in hippocampal pyramidal cells [Ito, I., Tanabe, S., Kohda, A. & Sugiyama, H. (1990) J. Physiol. (London) 424, 533-544] [33].

Gene context of QUISQUALIC ACID

• This effect was mimicked by (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG-I), a selective agonist of mGluR2/R3 receptors, but not by quisqualate at a concentration that stimulated inositol phosphate (InsP) synthesis, showing that mGluR1 and mGluR5 did not participate to this mechanism [34].
• Furthermore, the affinity of quisqualic acid at mGluR4 was increased to the same level as mGluR1 by the two double mutations, K74Y/K317R and K74Y/E287G [35].
• The mGlu5 receptor agonists (S)-3, 5-dihydroxyphenylglycine and quisqualate increased [(3)H-methyl]thymidine incorporation and melanocyte proliferation in subconfluent cultures, but impaired cell viability in confluent cultures [36].
• Current-clamp recordings (nystatin/perforated-patch method) were used to measure the membrane response of Purkinje neurons to brief microperfusion pulses (1.5 s) of the group I (mGluR1/mGluR5) agonists (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (300 microM), quisqualate (5 microM), and (R,S)-3,5-dihydroxyphenylglycine (50-500 microM) [37].
• At group I mGlu receptor expressing cells, LY341495 was micromolar potent in antagonizing quisqualate-induced phosphoinositide (PI) hydrolysis, with IC50 values of 7.8 and 8.2 microM for mGlu1a and mGlu5a receptors, respectively [38].

Analytical, diagnostic and therapeutic context of QUISQUALIC ACID

• After intracortical infusion of the NMDA receptor antagonist DL-2-amino-5-phosphonovalerate (DL-APV) for one day, iontophoretic responses to NMDA, to kainate, and to quisqualate revealed a receptor blockade specific to NMDA receptors and extending several millimeters from the cannula [39].
• Hours after thorough washout of exogenously added quisqualate, micromolar concentrations could be detected in the bathing medium by high performance liquid chromatography [40].
• Selective activation of NMDA receptors was achieved by deleting Mg2+ and including 3-10 microM glycine in the perfusion medium and by applying ligands in the presence of 30 microM quisqualate, which blocks the AMPA receptor and desensitizes the oocyte's own Ca(2+)-dependent Cl- current [41].
• Intraspinal injection of quisqualic acid (QUIS) produces an excitotoxic injury that leads to the onset of behavioral syndromes, believed to be related to the clinical condition of chronic pain [42].
• During EEG isoelectricity, AMPA binding was reduced by approximately 40%, which could represent quisqualate receptor desensitization [43].

References