Inhibition by chloral hydrate and trichloroethanol of AMPA-induced Ca(2+) influx in rat cultured cortical neurones.
The effects of chloral hydrate and its main metabolite 2,2, 2-trichloroethanol were investigated on the (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-induced rise of intracellular Ca(2+) concentration ([Ca(2+)](i)) in cultured non-pyramidal cortical neurones of rats by using single-cell fura-2 microfluorimetry. AMPA elicited a concentration-dependent effect that peaked at 300 microM (EC(50), 7. 5 microM). Responses to AMPA (30 microM) were markedly inhibited by superfusion with chloral hydrate (IC(50), 4.5 mM) or trichloroethanol (IC(50), 0.9 mM). By contrast, ethanol (100 mM) caused only slight inhibition. In conclusion, the results demonstrate that chloral hydrate and especially its metabolite trichloroethanol, inhibit the AMPA-induced rise of [Ca(2+)](i) by depressing the entry of Ca(2) into cortical neurones via the AMPA receptor-channel.
Fischer
W
W
Rudolf-Boehm-Institut für Pharmakologie und Toxikologie, Universität Leipzig, Härtelstr. 16-18, D-04107, Leipzig, Germany. fisw@medizin.uni-leipzig.de
Allgaier
C
C
Illes
P
P
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D002697:Chloral Hydrate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005023:Ethylene Chlorohydrin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005470:Fluorometry; D051381:Rats; D017208:Rats, Wistar; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000037:antagonists & inhibitors*
D002697:Chloral Hydrate; D005023:Ethylene Chlorohydrin; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C005849:2,2,2-trichloroethanol; D002118:Calcium