Quisqualic acid induced sensitization and the active uptake ofl-quisqualic acid by hippocampal slices

Schulte, Marvin K.; Roon, Robert J.; Koerner, James F.

doi:10.1016/0006-8993(93)91359-z

Cited by 16 publications

(10 citation statements)

References 17 publications

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“…This and the fact that none of the four compounds was able to reduce KYNA formation in tissue slices in the absence of extracellular Na + raised the possibility that some mGluR ligands can penetrate the cell membrane in a Na + ‐dependent fashion and subsequently attain higher intracellular concentrations to affect KAT II activity. Indeed, a rapid, concentrative quisqualate transport has been described in brain tissue, although the ion dependency of the process has so far not been examined (Schulte et al, 1993). It is notable that because the reduction of KYNA formation was not affected by the omission of Ca 2+ from the incubation buffer, the cellular uptake of these mGluR ligands does not appear to be linked to a Ca 2+ /Cl ‐ ‐dependent glutamate transporter (Foster and Fagg, 1984).…”

Section: Discussionmentioning

confidence: 99%

Some Metabotropic Glutamate Receptor Ligands Reduce Kynurenate Synthesis in Rats by Intracellular Inhibition of Kynurenine Aminotransferase II

Battaglia

Rassoulpour

et al. 2000

Journal of Neurochemistry

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Some metabotropic glutamate receptor (mGluR) ligands, such as quisqualate, L-(ϩ)-2-amino-4-phosphonobutyric acid (L-AP4), 4-carboxy-3-hydroxyphenylglycine (4C3HPG), and L-serine-O-phosphate (L-SOP), reduced the formation of the endogenous excitatory amino acid receptor antagonist kynurenate in brain and liver slices. The use of novel, subtype-selective mGluR agonists and antagonists excluded a role for any known mGluR subtype in this effect. The reduction of kynurenate formation was no longer observed when slices were incubated with the active mGluR ligands in the absence of extracellular Na ϩ . trans-Pyrrolidine-2,4-dicarboxylate (trans-PDC), a broad-spectrum ligand of Na ϩ -dependent glutamate transporters, was also able to reduce kynurenate formation. Quisqualate, 4C3HPG, L-AP4, and L-SOP did not further reduce kynurenate formation in the presence of trans-PDC, suggesting that the two classes of drugs may share the same mechanism of action. Hence, we hypothesized that the active mGluR ligands are transported inside the cell and act intracellularly to reduce kynurenate synthesis. We examined this possibility by assessing the direct effect of mGluR ligands on the activity of kynurenine aminotransferases (KATs) I and II, the enzymes that transaminate kynurenine to kynurenate. In brain tissue homogenates, KAT II (but not KAT I) activity was inhibited by quisqualate, 4C3HPG, L-AP4, L-SOP, and trans-PDC. Drugs that were unable to reduce kynurenate formation in tissue slices were inactive. We conclude that some mGluR ligands act intracellularly, inhibiting KAT II activity and therefore reducing kynurenate formation. This effect should be taken into consideration when novel mGluR ligands are developed for the treatment of neurological and psychiatric diseases.

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Section: Discussionmentioning

confidence: 99%

Some Metabotropic Glutamate Receptor Ligands Reduce Kynurenate Synthesis in Rats by Intracellular Inhibition of Kynurenine Aminotransferase II

Battaglia

Rassoulpour

et al. 2000

Journal of Neurochemistry

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“…IQuis is not likely to result from active uptake of quisqualate, as occurs with quisqualate sensitization of L-AP4 or L-AP5 responses in hippocampus (Charpak, Thompson, Giihwiler & Gerber, 1992;Schulte, Roon & Koerner, 1993). The sensitizing effect of quisqualate is observed in Ca2+-free solution, in low-Na+ solution, and when electrodes are filled with BAPTA (Charpak et al 1992).…”

Section: Discussionmentioning

confidence: 99%

Quisqualate‐preferring metabotropic glutamate receptor activates Na(+)‐Ca2+ exchange in rat basolateral amygdala neurones.

Keele

Arvanov

Shinnick‐Gallagher

1997

The Journal of Physiology

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1. Inward currents evoked by metabotropic glutamate receptor (mGlu) agonists quisqualate and 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) were characterized in the basolateral nucleus of the amygdala. Currents were recorded with whole-cell patch electrodes in the presence of D-2-amino-5-phosphonovaleric acid (D-APV, 50 uM), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 30 uM) and tetrodotoxin (TTX, 1 uM). 2. When recording with K+ electrodes, quisqualate (10-50 uM) produced an inward current which was not associated with a significant change in membrane slope conductance (Gm) and was insensitive to Ba2+ (0-2 mM) and Cs+ (2 mM). The 1S,3R-ACPD (50-200 /uM)-induced inward current was associated with a decreased 0m and reversed polarity around -95 mV.However, in BaP+ and Cs+, the 1S,3R-ACPD inward current amplitude was enhanced and was not accompanied by a change in Gm, a response similar to that evoked by quisqualate. 3. Glutamate (1 mM) and the group I mGlu specific agonist (S)-3,5-dihydroxyphenylglycine (DHPG, 100 sM) also evoked currents not associated with a change in Gm. 4. When recorded with Cs+ electrodes in external Ba2+ and Cs+ solution, quisqualate activated an inward current more potently than 1S,3R-ACPD, suggesting that this current is preferentially activated by quisqualate. The mGlu agonist-induced inward current was not accompanied by a Gm change under these conditions. 5. Substitution of extracellular Nae with Li+ (117 or 50 mM) or with 100 mm choline reduced the quisqualate-and IS,3R-ACPD-induced inward currents, results consistent with mediation by Na+-Ca2+ exchange. 6. The quisqualate-and IS,3R-ACPD-induced inward currents were reduced in Ca2+-free EGTA (1 mM) solution and prevented by including the Ca2P chelating agent BAPTA (10 mM) in the recording electrode. In low-Ca2+ (100 /M)-and Cd2+ (200 uM)-containing solution to block voltage-gated Ca2P currents, the quisqualate-induced current was not altered, but the 1S,3R-ACPD inward current was blocked. These data suggest that the quisqualate-and 1S,3R-ACPD-induced currents are mediated through a rise in intracellular Ca2+ and require extracellular Ca2+ but that the 1S,3R-ACPD current may depend on Ca2P influx via voltagegated Ca2P channels. 7. The quisqualate current with no Gm change was inhibited by including the Nae-Ca2P exchange inhibitory peptide (XIP; 10/uM) in the K+ recording electrode. XIP did not prevent the outward current evoked by baclofen (10 uM) or the 1S,3R-ACPD-induced inward current associated with decreased conductance.8. These data are consistent with the hypothesis that quisqualate and 1S,3R-ACPD in Ba2P and Cs+ solution activate a Na+-Ca2+ exchange current not associated with a conductance change. The quisqualate exchange current mediated through a group I mGlu may result from mobilization of Ca2+ from intracellular stores. The 1S,3R-ACPD exchange current requires extracellular Ca2+ passing through voltage-gated Ca2+ channels and may be mediated through a different receptor.

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“…The data show that the magnitude of the quisqualate-'primed' depolarizations obtained with L -A P~ is related to the concentrations of both quisqualate, as shown by Schulte et al (1993), and L-APQ administered to the slice. Furthermore the ~AP4-evoked depolarizations were inhibited by 1 pM NBQX.…”

Section: Discussionmentioning

confidence: 80%

Phenylglycines can Evoke Quisqualate‐primed Depolarizations in Rat Cingulate Cortex: An Effect Associated with [³H]DL‐AP₄ Uptake

Sheardown

Thomsen

1996

Eur J of Neuroscience

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Depolarization could be evoked in slices of rat cingulate cortex by the normally non-excitatory compound L-2-amino-4-phosphonobutyrate (L-AP4) if the slices had been sensitized by exposure to quisqualate. The magnitude of the response to L-AP4 was dependent on the concentrations of both L-AP4 and quisqualate and was inhibited by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor antagonism. A series of phenylglycine analogues were capable of evoking similar dose-dependent depolarizations in the rat cingulate cortex following quisqualate sensitization, the most potent being (S)-4-carboxy-3-hydroxyphenylglycine. If the superfusate collected during application of (S)-4-carboxy-3-hydroxyphenylglycine to a quisqualate-sensitized slice was administered to a slice not previously exposed to quisqualate, a small depolarization was obtained. All the compounds shown to be capable of evoking the quisqualate-sensitized response showed affinity for the L-AP4 uptake site whilst having no affinity at ionotropic glutamate receptors and different profiles of activity at metabotropic glutamate receptors. None of the compounds was active at the metabotropic glutamate 4a receptor. There was a statistically significant correlation between a compound's effectiveness in inhibiting [3H]DL-AP4 uptake into rat cortical synaptosomes and its potency in evoking quisqualate-sensitized depolarization. It is concluded that this response may be the result of hetero-exchange between L-AP4 ligands and quisqualate.

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Quisqualic acid induced sensitization and the active uptake ofl-quisqualic acid by hippocampal slices

Cited by 16 publications

References 17 publications

Some Metabotropic Glutamate Receptor Ligands Reduce Kynurenate Synthesis in Rats by Intracellular Inhibition of Kynurenine Aminotransferase II

Some Metabotropic Glutamate Receptor Ligands Reduce Kynurenate Synthesis in Rats by Intracellular Inhibition of Kynurenine Aminotransferase II

Quisqualate‐preferring metabotropic glutamate receptor activates Na(+)‐Ca2+ exchange in rat basolateral amygdala neurones.

Phenylglycines can Evoke Quisqualate‐primed Depolarizations in Rat Cingulate Cortex: An Effect Associated with [³H]DL‐AP₄ Uptake

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Quisqualic acid induced sensitization and the active uptake ofl-quisqualic acid by hippocampal slices

Cited by 16 publications

References 17 publications

Some Metabotropic Glutamate Receptor Ligands Reduce Kynurenate Synthesis in Rats by Intracellular Inhibition of Kynurenine Aminotransferase II

Some Metabotropic Glutamate Receptor Ligands Reduce Kynurenate Synthesis in Rats by Intracellular Inhibition of Kynurenine Aminotransferase II

Quisqualate‐preferring metabotropic glutamate receptor activates Na(+)‐Ca2+ exchange in rat basolateral amygdala neurones.

Phenylglycines can Evoke Quisqualate‐primed Depolarizations in Rat Cingulate Cortex: An Effect Associated with [3H]DL‐AP4 Uptake

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Phenylglycines can Evoke Quisqualate‐primed Depolarizations in Rat Cingulate Cortex: An Effect Associated with [³H]DL‐AP₄ Uptake