Identification, coassembly, and activity of γ-aminobutyric acid receptor subunits in renal proximal tubular cells

Satinder S. Sarang, Svetlana M. Lukyanova, Daniel D. Brown, Brian S. Cummings, Steven R. Gullans, Rick G. Schnellmann

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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 α1, α2, α4, α5, β1, γ1, γ2, and δ subunits in the kidney and to determine whether these subunits coassemble to form an active renal epithelial cell GABA A 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 α1, α5, β1, γ1, and γ2 subunits and that they were similar to the neuronal subunits. Sequencing of the PCR products revealed that the rabbit kidney cortex contained the α1 and γ2 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 α5, β1, and γ1. 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.

Original languageEnglish (US)
Pages (from-to)376-382
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume324
Issue number1
DOIs
StatePublished - Jan 2008
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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