Differential expression of γ-aminobutyric acid receptor A (GABA_A) and effects of homocysteine

Abstract

Background: γ-Aminobutyric acid (GABA) is a known inhibitory neurotransmitter in the mammalian central nervous system, and homocysteine (Hcy) behaves as an antagonist for GABA_A receptor. Although the properties and functions of GABA_A receptors are well studied in mouse neural tissue, its presence and significance in non-neural tissue remains obscure. The aim of the present study was to examine the expression of GABA_A receptor and its subunits in non-neural tissue.

Methods: The mice were analyzed. The presence of GABA_A receptor and its subunits was evaluated using Western blot and reverse transcription polymerase chain reaction.

Results: We report that GABA_A receptor protein is abundant in the renal medulla, cortex, heart, left ventricle, aorta and pancreas. Low levels of GABA_A receptor protein were detected in the atria of the heart, right ventricle, lung and stomach. The mRNA protein expression of GABA_A receptor subunit shows that α1, β1, β3 and γ1 subunits are present only in brain. The mRNA protein expression levels of GABA_A receptor α2, α6, β2 and γ3 subunits were highly expressed in brain compared to other tested tissue, while GABA_A receptor γ2 subunit was expressed only in brain and kidney. Treatment of microvascular endothelial cells with Hcy decreased GABA_A receptor protein level, which was restored to its baseline level in the presence of GABA_A receptor agonist, muscimol. The distribution of GABA_A and GABA_B receptors in wild type mice was determined and tissue-specific expression patterns were found showing that several receptor subtypes were also expressed in the central nervous system.

Conclusions: Hcy, a GABA_A agonist, was found to decrease GABA_A expression levels. These data enlarge knowledge on distribution of GABA receptors and give novel ideas of the effects of Hcy on different organs.

Clin Chem Lab Med 2007;45:1777–84.