The expression of GABA B1 and GABA B2 receptor subunits in the cNS differs from that in peripheral tissues

Abstract

GABA B receptors are G-protein-coupled receptors that mediate the slow and prolonged synaptic actions of GABA in the CNS via the modulation of ion channels. Unusually, GABA B receptors form functional heterodimers composed of GABA B1 and GABA B2 subunits. The GABA B1 subunit is essential for ligand binding, whereas the GABA B2 subunit is essential for functional expression of the receptor dimer at the cell surface. We have used real-time reverse transcriptase–polymerase chain reaction to analyse expression levels of these subunits, and their associated splice variants, in the CNS and peripheral tissues of human and rat. GABA B1 subunit splice variants were expressed throughout the CNS and peripheral tissues, whereas surprisingly GABA B2 subunit splice variants were neural specific. Using novel antisera specific to individual GABA B receptor subunits, we have confirmed these findings at the protein level. Analysis by immunoblotting demonstrated the presence of the GABA B1 subunit, but not the GABA B2 subunit, in uterus and spleen. Furthermore, we have shown the first immunocytochemical analysis of the GABA B2 subunit in the brain and spinal cord using a GABA B2-specific antibody. We have, therefore, identified areas of non-overlap between GABA B1 and GABA B2 subunit expression in tissues known to contain functional GABA B receptors. Such areas are of interest as they may well contain novel GABA B receptor subunit isoforms, expression of which would enable the GABA B1 subunit to reach the cell surface and form functional GABA B receptors.