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Identification of a GABAB Receptor Subunit, gb2, Required for Functional GABAB Receptor Activity
Open accessAbstract
G protein-coupled receptors are commonly thought to bind their cognate ligands and elicit functional responses primarily as monomeric receptors. In studying the recombinant gamma-aminobutyric acid, type B (GABAB) receptor (gb1a) and a GABAB-like orphan receptor (gb2), we observed that both receptors are functionally inactive when expressed individually in multiple heterologous systems. Characterization of the tissue distribution of each of the receptors by in situ hybridization histochemistry in rat brain revealed co-localization of gb1 and gb2 transcripts in many brain regions, suggesting the hypothesis that gb1 and gb2 may interact in vivo. In three established functional systems (inwardly rectifying K+ channel currents in Xenopus oocytes, melanophore pigment aggregation, and direct cAMP measurements in HEK-293 cells), GABA mediated a functional response in cells coexpressing gb1a and gb2 but not in cells expressing either receptor individually. This GABA activity could be blocked with the GABAB receptor antagonist CGP71872. In COS-7 cells coexpressing gb1a and gb2 receptors, co-immunoprecipitation of gb1a and gb2 receptors was demonstrated, indicating that gb1a and gb2 act as subunits in the formation of a functional GABAB receptor.
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Cited by
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Bowery, N. G., Bettler, B., Froestl, W., Gallagher, J. P., Marshall, F., Raiteri, M., Bonner, T. I., & Enna, S. J. (2002) · Pharmacological Reviews · doi:10.1124/pr.54.2.247 · Cited by 601
Self-citationDimerization: An Emerging Concept for G Protein–Coupled Receptor Ontogeny and Function
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Metadata
- Authors
- Ng, G. Y. K., Clark, J., Coulombe, N., Ethier, N., Hebert, T. E., Sullivan, R., Kargman, S., Chateauneuf, A., Tsukamoto, N., McDonald, T., Whiting, P., Mezey, É., Johnson, M. P., Liu, Q., Kolakowski, L. F., Evans, J. F., Bonner, T. I., & O'Neill, G. P.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-03
- Volume
- 274
- Issue
- 12
- Pages
- 7607-7610
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2101769320
- Cited by
- 212
- References
- 0
- FWCI
- 9.35
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- The paper
- Ng, G. Y. K., Clark, J., Coulombe, N., Ethier, N., Hebert, T. E., Sullivan, R., Kargman, S., Chateauneuf, A., Tsukamoto, N., McDonald, T., Whiting, P., Mezey, É., Johnson, M. P., Liu, Q., Kolakowski, L. F., Evans, J. F., Bonner, T. I., & O'Neill, G. P. (1999). Identification of a GABAB Receptor Subunit, gb2, Required for Functional GABAB Receptor Activity. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.274.12.7607
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