Molecular, functional, and pharmacological characterization of the metabotropic glutamate receptor type 5 splice variants: comparison with mGluR1

Abstract

This work was wppwted by grants from the CNRS, CEE (B102-CT93-0243), DRET (9 l/161) the Human Frontier5 Science Projiram (RG 5792B), and Bayer Company (Germany). This work has been d&e as part of the Bi oAveni n program supported by Rhone-Poul enc with the participation of the French Ministrv of Research and the French Ministrv of Industrv. J.G. was i supported by an IPSEN and then a Spnni\h governmen; fellowship\. We thank Dra. L. Journot and B. Chin! for critical reading of the manuscript, Dr. M. Lafon-Canal for the determlnatmn of the Glu ct&entrations, Dr. b. Jouhert for her hel p i n the confocal microscope cxperlmenta, and Dr. C. Romano for the gili of the mGluR5 antihwly Confocal microscopy experiments have been realired using the l'aulities of the Centre RCgional d'lmagerie Cel l ul ai re (C.R.I.C.). We thank also M. Passama and L. Charvet for their hel p i n the iconography. Correspondence shoul d be addressed to Dr. Jean-Phi l i ppe Pin, MCcanismes Mol&xdaires des Communications Cellulaires. 1JPR 902%CNRS, CCIPE, Rue de l a Cerdoni l l e 34OY4 Mtrntpellier Cetlex OS. France.

The Heptahelical Domain of GABAB2 Is Activated Directly by CGP7930, a Positive Allosteric Modulator of the GABAB Receptor

“…Although the mGlu5-truncated receptor displayed constitutive activity, no such activity could be detected with GABA B2 . This was in agreement with the higher constitutive activity measured with mGlu5 compared with GABA B receptor (51,52). However, in both cases, these HDs were activated by positive allosteric regulators CGP7930 and DFB for GABA B2 and mGlu5 HDs, respectively.…”

The activation mechanism of class-C G-protein coupled receptors

“…Because the VFTM of class-C GPCRs has been proposed to reach the closed (active) form in the absence of agonists, we were wondering whether this could be at the origin of constitutive activity of these receptors. When expressed in heterologous cells, both group-I mGluRs (mGlu1 and 5) display constitutive activity, as shown by the high basal IP formation measured in cells expressing these receptors compared to mock-transfected cells (Joly et al, 1995;Prézeau et al, 1996). However, such a constitutive activity was not inhibited by competitive antagonists that prevent the closure of the VFTM (Prézeau et al, 1996).…”

Metabotropic Glutamate Agonist-Induced Rotation: A Pharmacological, FOS Immunohistochemical, and [14C]-2-Deoxyglucose Autoradiographic Study

“…Group II (mGluRs 2 and 3) and group III (mGluRs 4 -8) receptors inhibit adenylyl cyclase, although with different pharmacological profiles (for review, see Pin and Duvosin, 1995;Roberts, 1995). Ligand-binding studies have shown the striatum to possess a high density of mGluR binding sites (Albin et al, 1992), and several mGluR mRNAs and proteins are expressed by striatal neurons, including members of all three mGluR groups (Abe et al, 1992;Martin et al, 1992;Shigemoto et al, 1992Shigemoto et al, , 1993Fotuhi et al, 1993;Ohishi et al, 1993a,b;Saugstead et al, 1994;Testa et al, 1994;Joly et al, 1995;Romano et al, 1995).…”