Microtubule depolymerization inhibits ethanol-induced enhancement of GABAA responses in stably transfected cells.
We studied whether microtubule organization is important for actions of ethanol on GABAA ergic responses by testing the effects of microtubule depolymerization on ethanol enhancement of GABA action in mouse L(tk-) cells stably transfected with GABAA receptor alpha 1 beta 1 gamma 2L subunits. The microtubule-disrupting agents colchicine, taxol, and vinblastine completely blocked ethanol-induced enhancement of muscimol-stimulated chloride uptake. beta-Lumicolchicine, a colchicine analogue that does not disrupt microtubules, had no effect on ethanol action. Colchicin did not alter the potentiating actions of flunitrazeparn or pentobarbital on muscimol-stimulated chloride uptakes. Thus, colchicine specifically inhibited the potentiating action of ethanol. From these findings, we conclude that intact microtubules are required for ethanol-induced enhancement of GABAA responses and suggest that a mechanism involving microtubules produces posttranslational modifications that are necessary for ethanol sensitivity in this cell system.
Whatley
V J
VJ
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262, USA.
Brozowski
S J
SJ
Hadingham
K L
KL
Whiting
P J
PJ
Harris
R A
RA
D000818:Animals; D002417:Cattle; D002460:Cell Line; D002712:Chlorides / Q000378:metabolism; D003078:Colchicine / Q000494:pharmacology; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005445:Flunitrazepam / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D009118:Muscimol / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D011108:Polymers / Q000378:metabolism*; D011940:Receptor Aggregation / Q000187:drug effects; D011963:Receptors, GABA-A / Q000378:metabolism*; D014162:Transfection
D002712:Chlorides; D011108:Polymers; D011963:Receptors, GABA-A; D009118:Muscimol; D000431:Ethanol; D005445:Flunitrazepam; D010424:Pentobarbital; D003078:Colchicine