The human GABAB1b and GABAB2 heterodimeric recombinant receptor shows low sensitivity to phaclofen and saclofen

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Abstract
The aim of this study was to characterize the pharmacological profile of the GABAB1/GABAB2 heterodimeric receptor expressed in Chinese hamster ovary (CHO) cells. We have compared receptor binding affinity and functional activity for a series of agonists and antagonists. The chimeric G‐protein, Gqi5, was used to couple receptor activation to increases in intracellular calcium for functional studies on the Fluorimetric Imaging Plate Reader (FLIPR), using a stable GABAB1/GABAB2/Gqi5 CHO cell line. [3H]‐CGP‐54626 was used in radioligand binding studies in membranes prepared from the same cell line. The pharmacological profile of the recombinant GABAB1/B2 receptor was consistent with that of native GABAB receptors in that it was activated by GABA and baclofen and inhibited by CGP‐54626A and SCH 50911. Unlike native receptors, the GABAB1/GABAB2/Gqi5 response was not inhibited by high microMolar concentration of phaclofen, saclofen or CGP 35348. This raises the possibility that the GABAB1/GABAB2/Gqi5 recombinant receptor may represent the previously described GABAB receptor subtype which is relatively resistant to inhibition by phaclofen. British Journal of Pharmacology (2000) 131, 1050–1054; doi:10.1038/sj.bjp.0703682