TY - JOUR T1 - The G Protein-Coupling Profile of Metabotropic Glutamate Receptors, as Determined with Exogenous G Proteins, Is Independent of Their Ligand Recognition Domain JF - Molecular Pharmacology JO - Mol Pharmacol SP - 778 LP - 786 DO - 10.1124/mol.53.4.778 VL - 53 IS - 4 AU - Marie-Laure Parmentier AU - Cécile Joly AU - Sophie Restituito AU - Joël Bockaert AU - Yves Grau AU - Jean-Philippe Pin Y1 - 1998/04/01 UR - http://molpharm.aspetjournals.org/content/53/4/778.abstract N2 - Metabotropic glutamate (mGlu), Ca2+-sensing, γ-aminobutyric acidB, and a large number of pheromone receptors constitute a peculiar family of G protein-coupled receptors. They possess a large extracellular domain that has been proposed to constitute their ligand binding domain. The aim of the current study was to examine whether this large ligand binding domain had any influence on the G protein-coupling selectivity of the receptor, and vice versa. We chose mGlu receptors, which are classified into three groups according to their sequence homology and pharmacology, as representatives of this receptor family. To define a G protein-coupling profile for these receptors, we used a set of exogenous phospholipase C-activating G proteins in the same way that synthetic ligands are used to define agonist and antagonist pharmacological profiles. This set includes Gα15, Gα16, Gαq, and chimeric Gαq proteins with the last few amino acids of either Gαi2 (Gαqi), Gαo(Gαqo), or Gαz (Gαqz). Cotransfection of mGlu receptors with these G proteins and examination of their coupling to phospholipase C revealed that group I, II, and III receptors have distinct G protein-coupling profiles. By swapping the extracellular domains of the most distantly related mGlu receptors (the rat group I mGlu1a and the Drosophila melanogaster group II DmGluA receptors), we show that the extracellular domain determines the agonist pharmacological profile and that this domain does not modify the G protein-coupling profile determined by the seven-transmembrane-domain region of mGlu receptors. ER -