The G Protein-Coupling Profile of Metabotropic Glutamate Receptors, as Determined with Exogenous G Proteins, Is Independent of Their Ligand Recognition Domain

1998 ◽  
Vol 53 (4) ◽  
pp. 778-786 ◽  
Author(s):  
Marie-Laure Parmentier ◽  
Cécile Joly ◽  
Sophie Restituito ◽  
Joël Bockaert ◽  
Yves Grau ◽  
...  
Keyword(s):  
Glutamate Receptors ◽  
G Protein ◽  
G Proteins ◽  
Metabotropic Glutamate Receptors ◽  
Ligand Recognition ◽  
G Protein Coupling ◽  
Protein Coupling ◽  
Metabotropic Glutamate

scholarly journals Positive and Negative Coupling of the Metabotropic Glutamate Receptors to a G Protein–activated K+ Channel, GIRK, in Xenopus Oocytes

1997 ◽  
Vol 109 (4) ◽  
pp. 477-490 ◽  
Author(s):  
Dahlia Sharon ◽  
Dmitry Vorobiov ◽  
Nathan Dascal
Keyword(s):  
Protein Kinase ◽  
Glutamate Receptors ◽  
G Protein ◽  
G Proteins ◽  
Metabotropic Glutamate Receptors ◽  
Xenopus Oocytes ◽  
K Channel ◽  
Metabotropic Glutamate ◽  
Girk Channel ◽  
The Brain

Metabotropic glutamate receptors (mGluRs) control intracellular signaling cascades through activation of G proteins. The inwardly rectifying K+ channel, GIRK, is activated by the βγ subunits of Gi proteins and is widely expressed in the brain. We investigated whether an interaction between mGluRs and GIRK is possible, using Xenopus oocytes expressing mGluRs and a cardiac/brain subunit of GIRK, GIRK1, with or without another brain subunit, GIRK2. mGluRs known to inhibit adenylyl cyclase (types 2, 3, 4, 6, and 7) activated the GIRK channel. The strongest response was observed with mGluR2; it was inhibited by pertussis toxin (PTX). This is consistent with the activation of GIRK by Gi/Go-coupled receptors. In contrast, mGluR1a and mGluR5 receptors known to activate phospholipase C, presumably via G proteins of the Gq class, inhibited the channel's activity. The inhibition was preceded by an initial weak activation, which was more prominent at higher levels of mGluR1a expression. The inhibition of GIRK activity by mGluR1a was suppressed by a broad-specificity protein kinase inhibitor, staurosporine, and by a specific protein kinase C (PKC) inhibitor, bis-indolylmaleimide, but not by PTX, Ca2+ chelation, or calphostin C. Thus, mGluR1a inhibits the GIRK channel primarily via a pathway involving activation of a PTX-insensitive G protein and, eventually, of a subtype of PKC, possibly PKC-μ. In contrast, the initial activation of GIRK1 caused by mGluR1a was suppressed by PTX but not by the protein kinase inhibitors. Thus, this activation probably results from a promiscuous coupling of mGluR1a to a Gi/Go protein. The observed modulations may be involved in the mGluRs' effects on neuronal excitability in the brain. Inhibition of GIRK by phospholipase C–activating mGluRs bears upon the problem of specificity of G protein (GIRK interaction) helping to explain why receptors coupled to Gq are inefficient in activating GIRK.

G-protein-independent signaling mediated by metabotropic glutamate receptors

10.1038/15996 ◽  
1999 ◽  
Vol 2 (12) ◽  
pp. 1070-1077 ◽  
Author(s):  
Christian Heuss ◽  
Massimo Scanziani ◽  
Beat H. Gähwiler ◽  
Urs Gerber
Keyword(s):  
Glutamate Receptors ◽  
G Protein ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate

scholarly journals Coupling of D2 dopamine receptors to G-proteins in solubilized preparations of bovine caudate nucleus

1992 ◽  
Vol 281 (2) ◽  
pp. 369-375 ◽  
Author(s):  
J A Chazot ◽  
P G Strange
Keyword(s):  
Ionic Strength ◽  
Caudate Nucleus ◽  
Dopamine Receptors ◽  
G Protein ◽  
G Proteins ◽  
Gel Filtration ◽  
D2 Dopamine Receptors ◽  
G Protein Coupling ◽  
Protein Coupling ◽  
Primary Determinant

1. The coupling of D2 dopamine receptors and G-proteins has been examined in cholate-solubilized preparations of bovine caudate nucleus. 2. No receptor-G-protein coupling could be detected in solubilized preparations obtained in 0.3% cholate, but if this preparation is diluted 5-fold, coupling is re-established. 3. The dilution process was examined, and it was shown that the change in ionic strength was an important factor in modulating the observed receptor-G-protein interaction. 4. Ionic strength was shown, however, not to be the primary determinant of receptor-G-protein coupling. This is likely to be the formation, upon dilution of the preparation, of vesicles in which receptor and G-protein reassociate. 5. The formation of vesicles upon dilution was examined by a variety of techniques, including thermal-stability studies, gel filtration, centrifugation and electron microscopy.

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