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Vol. 63, Issue 1, 183-191, January 2003

Specificity of Metabotropic Glutamate Receptor 2 Coupling to G Proteins

Paul J. Kammermeier, Margaret I. Davis, and Stephen R. Ikeda

Laboratory of Molecular Physiology (P.J.K., S.R.I.) and Laboratory of Integrative Neuroscience (M.I.D.), National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland

Metabotropic glutamate receptor 2 (mGluR2) is a class 3 G protein-coupled receptor and an important mediator of synaptic activity in the central nervous system. Previous work demonstrated that mGluR2 couples to pertussis toxin (PTX)-sensitive G proteins. However, the specificity of mGluR2 coupling to individual members of the Gi/o family is not known. Using heterologously expressed mGluR2 in rat sympathetic neurons from the superior cervical ganglion (SCG), the mGluR2/G protein coupling profile was characterized by reconstituting coupling in PTX-treated cells expressing PTX-insensitive mutant Galpha proteins and Gbeta gamma . By employing this method, it was demonstrated that mGluR2 coupled strongly with Galpha ob, Galpha i1, Galpha i2, and Galpha i3, although coupling to Galpha oa was less efficient. In addition, mGluR2 did not seem to couple to the most divergent member of the Gi/o family, Galpha z, although Galpha z coupled strongly to the endogenous alpha 2 adrenergic receptor. To determine which Galpha proteins may be natively expressed in SCG neurons, the presence of mRNA for various Galpha proteins was tested using reverse transcription-polymerase chain reaction. Strong bands were detected for all members of the Gi/o family (Galpha o, Galpha i1, Galpha i2, Galpha i3, Galpha z) as well as for Galpha 11 and Galpha s. A weak signal was detected for Galpha q and no Galpha 15 mRNA was detected.

Copyright © 2003 by U.S. Government


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