Identification of the gamma-aminobutyric acid receptor beta(2) and beta(3)subunits in rat, rabbit, and human kidneys

The properties and functions of gamma -aminobutyric acid (GABA(A)) receptor s in the mammalian central nervous system are well studied. However, the pr esence and significance of GABA(A) receptors in nonneural tissue is less cl ear. The goal of this study was to examine the expression and localization of the GABA(A) receptor beta (2) and beta (3) subunits in the kidney. Rever se transcriptase products from RNA isolated from rat and rabbit kidney cort ex and cerebellum and rabbit S-2 segments were amplified by use of PCR and GABA(A) beta (2) and beta (3) subunit-specific primers. Sequencing of the k idney PCR products revealed that the rat kidney cortex and rat neuronal GAB A(A) receptor beta (2) subunit were identical in nucleotide composition. Th e rabbit kidney and rabbit neuronal GABA(A) receptor beta (2) subunit were 99% identical in nucleotide composition. Sequencing of the kidney PCR produ cts revealed that the rat kidney cortex and rat neuronal GABA(A) receptor b eta (3) subunits were 93% and 95% identical in nucleotide and amino acid co mposition, and rabbit kidney cortex and rabbit neuronal GABA(A) receptor be ta (3) subunits were 95% and 98% identical in nucleotide and amino acid com position, respectively. PCR screening of a human kidney cDNA library and se quencing,revealed that the human kidney cortex and neuronal beta (3) subuni ts were identical in nucleotide composition. Immunoblot analysis of rat kid ney cortex and brain identified immunoreactive proteins in the 55 to 57 kD region: corresponding to the GABA(A) receptor beta (2) and beta (3) subunit s. Immunohistochemistry revealed cytosolic and basolateral staining of the proximal convoluted and straight tubule. These results provide compelling e vidence for the expression of the GABA(A) receptor beta (2) and beta (3) su bunits in the kidney of multiple species and the localization of the beta ( 2)/beta (3) subunits to the renal proximal tubule.