Excitatory Amino Acid‐Induced Toxicity in Chick Retina: Amino Acid Release, Histology, and Effects of Chloride Channel Blockers

Excitatory Amino Acid‐Induced Toxicity in Chick Retina: Amino Acid Release, Histology, and... Abstract: Acute excitotoxicity in embryonic chick retina and the ability of C1− channel blockers to prevent toxicity were evaluated by measurement of endogenous amino acid release and histology. Treatment of retina with kainate, quisqualate, or N‐methyl‐D‐aspartate resulted in a large dose‐dependent release of γ‐aminobutyric acid and taurine, moderate release of glutamine and alanine, and no measurable release of glu‐tamate or aspartate. Concentrations inducing maximal γ‐aminobutyric acid release were 50 μM quisqualate, 100 μM kainate, and 100 μM N‐methyl‐D‐aspartate. Treatment with 1 mM glutamate resulted in significant γ‐aminobutyric acid release, as well as an elevation in medium aspartate levels. Typical excitotoxic retinal lesions were produced by the agonists and, at the lower concentrations tested, revealed a regional sensitivity. There was a positive correlation between the amount of γ‐aminobutyric acid release and the extent of tissue swelling, suggesting that release may be secondary to toxic cellular events. Omission of C1− completely blocked cytotoxic effects due to kainate or glutamate. Likewise, addition of the C1−/bicarbonate anion channel blocker 4,4′‐di‐isothiocyanatostilbene‐2,2′‐disulfonate at 600 μM protected retina from cytotoxic damage from all excitotoxic analogs and restored amino acid levels to baseline values. Furosemide. which blocks Na+/K+/2C1− cotransport, was only minimally effective in reducing amino acid release induced by the agonists. Consistent with the latter, histological examination showed the continued presence of the lesion but with general reduction of cellular edema. These results indicate that although influx of C1− is a central component of the acute excitotoxic phenomenon, mechanisms other than passive Cl−flux may be involved. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neurochemistry Wiley

Excitatory Amino Acid‐Induced Toxicity in Chick Retina: Amino Acid Release, Histology, and Effects of Chloride Channel Blockers

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Publisher
Wiley
Copyright
Copyright © 1989 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0022-3042
eISSN
1471-4159
D.O.I.
10.1111/j.1471-4159.1989.tb08559.x
Publisher site
See Article on Publisher Site

Abstract

Abstract: Acute excitotoxicity in embryonic chick retina and the ability of C1− channel blockers to prevent toxicity were evaluated by measurement of endogenous amino acid release and histology. Treatment of retina with kainate, quisqualate, or N‐methyl‐D‐aspartate resulted in a large dose‐dependent release of γ‐aminobutyric acid and taurine, moderate release of glutamine and alanine, and no measurable release of glu‐tamate or aspartate. Concentrations inducing maximal γ‐aminobutyric acid release were 50 μM quisqualate, 100 μM kainate, and 100 μM N‐methyl‐D‐aspartate. Treatment with 1 mM glutamate resulted in significant γ‐aminobutyric acid release, as well as an elevation in medium aspartate levels. Typical excitotoxic retinal lesions were produced by the agonists and, at the lower concentrations tested, revealed a regional sensitivity. There was a positive correlation between the amount of γ‐aminobutyric acid release and the extent of tissue swelling, suggesting that release may be secondary to toxic cellular events. Omission of C1− completely blocked cytotoxic effects due to kainate or glutamate. Likewise, addition of the C1−/bicarbonate anion channel blocker 4,4′‐di‐isothiocyanatostilbene‐2,2′‐disulfonate at 600 μM protected retina from cytotoxic damage from all excitotoxic analogs and restored amino acid levels to baseline values. Furosemide. which blocks Na+/K+/2C1− cotransport, was only minimally effective in reducing amino acid release induced by the agonists. Consistent with the latter, histological examination showed the continued presence of the lesion but with general reduction of cellular edema. These results indicate that although influx of C1− is a central component of the acute excitotoxic phenomenon, mechanisms other than passive Cl−flux may be involved.

Journal

Journal of NeurochemistryWiley

Published: Nov 1, 1989

References

  • Mechanism of kainate toxicity to cerebellar neurons in vitro is analogous to reperfusion tissue injury
    Dykens, Dykens; Stern, Stern; Trenkner, Trenkner
  • Action of the neurotoxin kainic acid on high affinity uptake of L‐glutamic acid in rat brain slices
    Johnston, Johnston; Kennedy, Kennedy; Twitchin, Twitchin
  • L‐Phenylalanyl‐L‐glutamate‐stimulated, chloride‐dependent glutamate binding represents glutamate sequestration mediated by an exchange system
    Kessler, Kessler; Petersen, Petersen; Vu, Vu; Baudry, Baudry; Lynch, Lynch
  • Alteration in neuronal‐glial metabolism of glutamate by the neurotoxin kainic acid
    Krespan, Krespan; Berl, Berl; Nicklas, Nicklas
  • Effect of selective kainate lesions on the release of glutamate and aspartate from chick retina.
    Lopez‐Colome, Lopez‐Colome; Somohano, Somohano
  • Carbonic anhydrase: Chemistry, physiology and inhibition
    Maren, Maren
  • Glutamate uptake and metabolism in C‐6 glioma cells: alterations by potassium ion and dibutyryl camp
    Nicklas, Nicklas; Browning, Browning

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