Altered receptor subtypes in the forebrain of GABA(A) receptor delta subunit-deficient mice: recruitment of gamma 2 subunits

Neuroscience
E R KorpiH Lüddens

Abstract

A GABA(A) receptor delta subunit-deficient mouse line was created by homologous recombination in embryonic stem cells to investigate the role of the subunit in the brain GABA(A) receptors. High-affinity [(3)H]muscimol binding to GABA sites as studied by ligand autoradiography was reduced in various brain regions of delta(-/-) animals. [(3)H]Ro 15-4513 binding to benzodiazepine sites was increased in delta(-/-) animals, partly due to an increment of diazepam-insensitive receptors, indicating an augmented forebrain assembly of gamma 2 subunits with alpha 4 subunits. In the western blots of forebrain membranes of delta(-/-) animals, the level of gamma 2 subunit was increased and that of alpha 4 decreased, while the level of alpha1 subunits remained unchanged. In the delta(-/-) forebrains, the remaining alpha 4 subunits were associated more often with gamma 2 subunits, since there was an increase in the alpha 4 subunit level immunoprecipitated by the gamma 2 subunit antibody. The pharmacological properties of t-butylbicyclophosphoro[(35)S]thionate binding to the integral ion-channel sites were slightly altered in the forebrain and cerebellum, consistent with elevated levels of alpha 4 gamma 2 and alpha 6 gamma 2 subunit-containing ...Continue Reading

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Citations

Mar 20, 2004·Pharmacology & Therapeutics·Janine L Steiger, Shelley J Russek
Jul 31, 2003·Life Sciences·David R Burt
Jun 5, 2003·Pharmacology & Therapeutics·Jean-Marc Fritschy, Ina Brünig
Jul 20, 2002·Progress in Neurobiology·Esa R KorpiHartmut Lüddens
Dec 25, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Dev ChandraEsa R Korpi
Apr 3, 2008·Nature Reviews. Neuroscience·Tija C JacobRachel Jurd
May 23, 2003·The New England Journal of Medicine·Jason A CampagnaStuart A Forman
Oct 1, 2013·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Elena VashchinkinaEsa R Korpi
Sep 29, 2006·Proceedings of the National Academy of Sciences of the United States of America·D ChandraG E Homanics
Nov 19, 2003·Proceedings of the National Academy of Sciences of the United States of America·Brandon M StellIstvan Mody
Apr 1, 2009·Neuropharmacology·David A MathersErnest Puil
Sep 10, 2004·The European Journal of Neuroscience·J Martin VerkuylMarian Joëls
Jun 28, 2005·The European Journal of Neuroscience·D W CopeM Capogna
Dec 14, 2007·Alcoholism, Clinical and Experimental Research·Dev ChandraGregg E Homanics
Oct 7, 2004·European Journal of Pharmacology·Anthony S BasilePhil Skolnick
Sep 17, 2004·Pharmacology & Therapeutics·Stefano Vicini, Pavel Ortinski
Sep 27, 2005·Molecular and Cellular Neurosciences·S B ChristieA L De Blas
Jul 6, 2005·Pharmacology & Therapeutics·Esa R Korpi, Saku T Sinkkonen
Aug 17, 2014·Neuropharmacology·Paul D WhissellBeverley A Orser
Sep 2, 2008·Neuropharmacology·Richard W Olsen, Werner Sieghart
Jul 4, 2006·Pharmacology & Therapeutics·Martin WallnerRichard W Olsen

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