The human GABA B1b and GABA B2 heterodimeric recombinant receptor shows low sensitivity to phaclofen and saclofen

The aim of this study was to characterize the pharmacological profile of the GABA B1 /GABA B2 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, G qi5 , was used to couple receptor activation to increases in intracellular calcium for functional studies on the Fluorimetric Imaging Plate Reader (FLIPR), using a stable GABA B1 /GABA B2 /G qi5 CHO cell line. [ 3 H]‐CGP‐54626 was used in radioligand binding studies in membranes prepared from the same cell line. The pharmacological profile of the recombinant GABA B1/B2 receptor was consistent with that of native GABA B receptors in that it was activated by GABA and baclofen and inhibited by CGP‐54626A and SCH 50911. Unlike native receptors, the GABA B1 /GABA B2 /G qi5 response was not inhibited by high microMolar concentration of phaclofen, saclofen or CGP 35348. This raises the possibility that the GABA B1 /GABA B2 /G qi5 recombinant receptor may represent the previously described GABA B receptor subtype which is relatively resistant to inhibition by phaclofen.British Journal of Pharmacology (2000) 131 , 1050–1054; doi: 10.1038/sj.bjp.0703682