Ethanol, flunitrazepam, and pentobarbital modulation of GABAA receptors expressed in mammalian cells and Xenopus oocytes

Alcoholism, Clinical and Experimental Research
R A HarrisP Whiting

Abstract

GABAA receptors composed of human alpha 1 beta 2 gamma 2L, alpha 1 beta 2 gamma 2S, alpha 1 beta 3 gamma 2S, alpha 6 beta 3 gamma 2S, and alpha 5 beta 3 gamma 3 subunits as well as bovine alpha 1 beta 1 gamma 2L and alpha 1 beta 1 subunits were stably expressed in mammalian L(tk-) cells and transiently expressed in Xenopus oocytes. Effects of muscimol, ethanol, flunitrazepam, and pentobarbital on receptor function were compared for the two expression systems using a 36Cl- flux assay for cells and an electrophysiological assay for oocytes. Muscimol activated all receptors in both expression systems but was more potent for L(tk-) cells than oocytes; this difference ranged from 2.6-to 26-fold, depending upon subunit composition. The most pronounced differences between receptors and expression systems were found for ethanol. In L(tk-) cells, low (5-50 mM) concentrations of ethanol potentiated muscimol responses only with receptors containing the gamma 2L subunit. In oocytes, concentrations of 30-100 mM produced small enhancements for most subunit combinations. Flunitrazepam enhanced muscimol responses for all receptors except alpha 6 beta 3 gamma 2S and alpha 1 beta 1, and this enhancement was similar for both expression systems. P...Continue Reading

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Citations

Sep 9, 2004·Alcohol·Sheryl S SmithMaria Gulinello
Mar 5, 1999·Journal of Neuroscience Methods·M J WickC F Valenzuela
Jan 5, 2000·Neuroscience Research·M K Akinci, P R Schofield
Jul 16, 1999·Neurochemistry International·S J Mihic
Jul 22, 1998·Progress in Neurobiology·C L FaingoldA Riaz
Aug 26, 1998·Drug and Alcohol Dependence·R A HarrisC F Valenzuela
Oct 24, 1998·British Journal of Pharmacology·M P MasciaR A Harris
Jun 29, 1999·British Journal of Pharmacology·S UenoR A Harris
Apr 28, 2005·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Hugh E Criswell, George R Breese
May 23, 2003·The New England Journal of Medicine·Jason A CampagnaStuart A Forman
Apr 25, 2008·The Journal of Pharmacology and Experimental Therapeutics·Takafumi Horishita, R Adron Harris
Nov 26, 2009·Anesthesia and Analgesia·Yun WengJames M Sonner
Sep 17, 2011·Alcoholism, Clinical and Experimental Research·Chupong IttiwutJoel Gelernter
Aug 7, 2013·Alcoholism, Clinical and Experimental Research·Jennifer L HelferBrian R Christie
Sep 20, 2011·Drug and Alcohol Dependence·Keith L Shelton, Katherine L Nicholson
Sep 3, 1998·Alcoholism, Clinical and Experimental Research·C F ValenzuelaR A Harris
Aug 3, 2000·Alcoholism, Clinical and Experimental Research·T MoriT Narahashi
Oct 2, 1998·Alcoholism, Clinical and Experimental Research·C F ValenzuelaK M Nixon
Nov 5, 1999·Alcoholism, Clinical and Experimental Research·R A Harris
Apr 9, 1999·Anesthesia and Analgesia·E I EgerT Hudlicky
Nov 20, 2002·The Journal of Pharmacology and Experimental Therapeutics·T L CrowderJ L Weiner
Nov 8, 2005·The Journal of Pharmacology and Experimental Therapeutics·Cecilia M BorgheseR Adron Harris
Jun 26, 2003·Alcoholism, Clinical and Experimental Research·Gene-Jack WangYeming Ma
Feb 15, 2003·Biological Research for Nursing·Joan A Masters, Joanne S Stevenson
Jan 1, 1999·Trends in Pharmacological Sciences·L J ChandlerF T Crews

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