Vol. 305, Issue 1, 191-196, April 2003

Differential Regulation of GABA_B Receptor Subunit Expression and Function

S. A. Sands, K. E. McCarson and S. J. Enna

Department of Pharmacology, Toxicology and Therapeutics, Kansas University School of Medicine, Kansas City, Kansas

The GABA_B receptor is a G protein-coupled heterodimer composed of GABA_B1 and GABA_B2 subunits. In the present study, experiments were undertaken to examine the relationship between GABA_B receptor function and subunit expression in the rat lumbar spinal cord following pharmacological and physiological manipulation of this receptor system. Although formalin-induced hind paw inflammation increases the production of GABA_B1 and GABA_B2 protein in the spinal cord within 24 h, there is no change in receptor function, as measured by the baclofen-stimulated guanosine 5'-O-(3-[³⁵S]thiotriphosphate) ([³⁵S]GTPS) binding assay. Conversely, although chronic (7 days) administration of baclofen, a GABA_B receptor agonist, abolishes baclofen-stimulated [³⁵S]GTPS binding in the spinal cord tissue, causes tolerance to the sedative and antinociceptive effects of the drug, increases the number of formalin-induced hind paw flinches, and induces mechanical hyperalgesia, this treatment had no effect on the levels of GABA_B1 or GABA_B2 mRNAs in the lumbar spinal cord. The results indicate a lack of concordance between expression of GABA_B1 and GABA_B2 subunits and GABA_B receptor function, suggesting these subunit proteins may serve multiple functions in the cells. Moreover, these findings indicate that nongenomic mechanisms are primarily responsible for the GABA_B receptor desensitization that occurs during prolonged exposure to receptor agonist.