Quinolinic acid but not MK-801 protects the dopaminergic system from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced toxicity in goldfish retina.
The toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, intravitreally injected in goldfish eye, involves interplexiform retinal neurons and depletes tyrosine hydroxylase immunoreactivity and dopamine levels. This induced neurotoxicity was prevented by the concomitant administration in non-toxic doses (10 micrograms) of quinolinic acid, an endogenous structural analogue of N-methyl D-aspartate with excitotoxic properties. Quinolinic acid is ineffective on the retinal degeneration induced by 1-methyl-4-phenylpyridinium ion. This fact suggests that quinolinic acid inhibits the MAO-B oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. MK-801, a noncompetitive antagonist of glutamate NMDA-receptors, exerts partial protective effects on MPTP-induced delayed toxicity in mammals. In the goldfish eye, MK-801, injected in low concentration, and in conjunction with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine or 1-methyl-4-phenylpyridinium ion, did not prevent retinal neurodegeneration. Ten micrograms of MK-801 alone did not affect retinal neurons, while a higher concentration (20 micrograms) causes the chromatolysis of some photoreceptor nuclei.
Guarnieri
T
T
Department of Biology, University of Bologna, Italy.
Virgili
M
M
Carraro
S
S
Villani
L
L
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors; D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D006054:Goldfish; D020267:MPTP Poisoning; D008854:Microscopy, Electron; D009336:Necrosis; D009474:Neurons / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D010786:Photoreceptor Cells / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D017378:Quinolinic Acid / Q000494:pharmacology*; D012160:Retina / Q000187:drug effects / Q000473:pathology*
D016291:Dizocilpine Maleate; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D017378:Quinolinic Acid; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine