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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on October 24, 2007; DOI: 10.1124/jpet.107.129957

0022-3565/08/3241-376-382$20.00
JPET 324:376-382, 2008
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GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Identification, Coassembly, and Activity of {gamma}-Aminobutyric Acid Receptor Subunits in Renal Proximal Tubular Cells

Satinder S. Sarang, Svetlana M. Lukyanova1, Daniel D. Brown, Brian S. Cummings2, Steven R. Gullans, and Rick G. Schnellmann

Harvard Center for Neurologic Diseases, Brigham and Women's Hospital, Cambridge, Massachusetts (S.S.S., S.R.G.); Department of Pharmaceutical Sciences, Medical University of South Carolina, Charleston, South Carolina (S.M.L., B.S.C., R.G.S.); and National Institutes of Environmental Health Sciences, Research Triangle Park, North Carolina (D.D.B.)

Although the properties and functions of GABAA receptors in the mammalian central nervous system have been well studied, the presence and significance of GABAA receptors in non-neural tissues are less clear. The goal of this study was to examine the expression of GABAA receptor {alpha}1, {alpha}2, {alpha}4, {alpha}5, β1, {gamma}1, {gamma}2, and {delta} subunits in the kidney and to determine whether these subunits coassemble to form an active renal epithelial cell GABAA receptor. Using reverse transcriptase products from RNA isolated from rat and rabbit kidney cortex and brain or cerebellum through polymerase chain reaction (PCR) and sequencing of the PCR products, we revealed that rat kidney cortex contained the {alpha}1, {alpha}5, β1, {gamma}1, and {gamma}2 subunits and that they were similar to the neuronal subunits. Sequencing of the PCR products revealed that the rabbit kidney cortex contained the {alpha}1 and {gamma}2 subunits and that they were similar to their neuronal counterparts. Immunoprecipitation and immunoblot studies using GABAA receptor subunit-specific antibodies and detergent-solubilized rat kidney cortex membranes identified a GABAA receptor complex containing {alpha}5, β1, and {gamma}1. Isolated rat renal proximal tubular cells exhibited GABA-mediated, picrotoxin-sensitive 36Cl- uptake. These studies demonstrate the presence of numerous GABAA receptor subunits in the kidneys of two species, the assembly of the subunits into at least one novel receptor complex, and an active GABAA receptor in renal proximal tubular cells.

Received August 17, 2007; accepted October 22, 2007.

Address correspondence to: Dr. Rick G. Schnellmann, Department of Pharmaceutical Sciences, Medical University of South Carolina, 280 Calhoun St., POB 250140, Charleston, SC 29425. E-mail: schnell{at}musc.edu






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