Kainate-induced retina amacrine-like cell damage is mediated by AMPA receptors.
We investigated the effect of domoate, kainate and AMPA on 45Ca2+ uptake and on metabolic activity of cultured chick amacrine-like cells, as measured by reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Domoate and kainate stimulated 45Ca2+ uptake and decreased MTT reduction, in a LY 303070-sensitive manner. AMPA caused a small increase on 45Ca2+ uptake, but it was without effect on MTT reduction. AMPA reduced both the 45Ca2+ entry and neurotoxicity induced by kainate, and cyclothiazide enhanced both the 45Ca2+ entry and neurotoxicity induced by AMPA. The results indicate that the AMPA receptors are the non-NMDA glutamate receptors involved in excitotoxicity.
Ferreira
I L
IL
Center for Neuroscience of Coimbra, Department of Zoology, University of Coimbra, Portugal.
Duarte
C B
CB
Carvalho
A P
AP
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology; D001581:Benzothiadiazines / Q000494:pharmacology; D002132:Calcium Radioisotopes / Q000493:pharmacokinetics; D002478:Cells, Cultured; D002645:Chickens; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D018091:Receptors, AMPA / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000502:physiology; D012160:Retina / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D000959:Antihypertensive Agents; D001569:Benzodiazepines; D001581:Benzothiadiazines; D002132:Calcium Radioisotopes; D016291:Dizocilpine Maleate; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007608:Kainic Acid; D009467:Neuromuscular Depolarizing Agents; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C079692:GYKI 53655; C012301:domoic acid; C004639:cyclothiazide