title: Microtubule depolymerization inhibits ethanol-induced enhancement of GABAA responses in stably transfected cells.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262, USA.
authors.forename: V J
authors.initials: VJ
authors.lastname: Whatley
authors.forename: S J
authors.initials: SJ
authors.lastname: Brozowski
authors.forename: K L
authors.initials: KL
authors.lastname: Hadingham
authors.forename: P J
authors.initials: PJ
authors.lastname: Whiting
authors.forename: R A
authors.initials: RA
authors.lastname: Harris
mesh_terms: 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
chemical_list: D002712:Chlorides; D011108:Polymers; D011963:Receptors, GABA-A; D009118:Muscimol; D000431:Ethanol; D005445:Flunitrazepam; D010424:Pentobarbital; D003078:Colchicine