Abstract：
:The GABA(B) receptor was the first heteromeric G-protein coupled receptor (GPCR) identified. Indeed, both GABA(B1) and GABA(B2) subunits appear necessary to get a functional GABA(B) receptor. Soon after the cloning of both subunits, it was demonstrated that GABA(B2) was required for GABA(B1) to reach the cell surface. However, even a mutated GABA(B1) able to reach the cell surface is not functional alone despite its ability to bind GABA(B) ligands. This clearly demonstrated that GABA(B2) is not only required for the correct trafficking of GABA(B1) but also for the correct functioning of the receptor. In the present review article, we will summarize our actual knowledge of the specific role of each subunit in ligand recognition, intramolecular transduction, G-protein activation and allosteric modulation. We will show that the GABA(B) receptor is an heterodimer (not an hetero-oligomer), that agonists bind in GABA(B1), whereas GABA(B2) controls agonist affinity and is responsible for G-protein coupling. Finally, we will show that the recently identified positive allosteric modulator CGP7930 acts as a direct activator of the heptahelical domain of GABA(B2), being therefore the first GABA(B2) ligand identified so far.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Pin JP,Kniazeff J,Binet V,Liu J,Maurel D,Galvez T,Duthey B,Havlickova M,Blahos J,Prézeau L,Rondard Pdoi
10.1016/j.bcp.2004.06.035subject
Has Abstractpub_date
2004-10-15 00:00:00pages
1565-72issue
8eissn
0006-2952issn
1873-2968pii
S0006-2952(04)00525-8journal_volume
68pub_type
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