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The human GABA B1b and GABA B2 heterodimeric recombinant receptor shows low sensitivity to phaclofen and saclofen
Author(s) -
Wood M D,
Murkitt K L,
Rice S Q,
Testa T,
Punia P K,
Stammers M,
Jenkins O,
Elshourbagy N A,
Shabon U,
Taylor S J,
Gager T L,
Minton J,
Hirst W D,
Price G W,
Pangalos M
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703682
Subject(s) - chinese hamster ovary cell , receptor , gabaa receptor , gaba receptor , biology , gabab receptor , chemistry , medicine , biochemistry , pharmacology
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