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GABBR2  -  gamma-aminobutyric acid (GABA) B receptor, 2

Homo sapiens

Synonyms: G-protein coupled receptor 51, GABA-B receptor 2, GABA-B-R2, GABA-BR2, GABABR2, ...
 
 
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Disease relevance of GABBR2

 

Psychiatry related information on GABBR2

 

High impact information on GABBR2

  • Studies with Daudi cells and glycosphingolipid-deficient Daudi mutants and U937 cells identified that the presence of Gb2/Gb3 correlates with IFN-alpha sensitivity [4].
  • We have identified a gene encoding a GABAB receptor, the human GABABR2, located on chromosome 9q22.1, that is distinct from the recently reported rat GABABR1 [5].
  • GABABR2 is localized to the cell surface in transfected COS cells, and negatively couples to adenylyl cyclase in response to GABA, baclofen, and 3-aminopropyl(methyl)phosphinic acid in CHO cells lacking GABABR1 [5].
  • Identification of a functional homomeric GABABR2 coupled to adenylyl cyclase suggests that the complexity of GABAB pharmacological data is at least in part due to the presence of more than one receptor and opens avenues for future research leading to an understanding of metabotropic GABA receptor signal transduction mechanisms [5].
  • The Gpr51 protein was upregulated by nicotine in the amygdala (26%), striatum (73%), PFC (28%), and medial basal hypothalamus (MBH; 19%) but downregulated in the NA (-72%) [3]
  • Common genetic variations in the GABBR2 gene contribute to the risk of Mesial Temporal Lobe Epilepsy. Patients carrying a particular haplotype of GABBR2 exhibited an earlier onset of MTLE [6].
 

Biological context of GABBR2

 

Anatomical context of GABBR2

 

Associations of GABBR2 with chemical compounds

  • Importantly, GABABR2 receptors can form a heteromeric assembly with GABABR1 proteins to operate as a heterodimer that displays robust coupling to inward-rectifying K+ channels, as well as inhibition of forskolin-stimulated adenylate cyclase activity [8].
 

Other interactions of GABBR2

  • In contrast, isolated GABAB-R1 peptides folded into relatively unstable homodimers, whereas GABAB-R2 peptides were largely unstructured [1].
  • 1. In this study we report a new assay of heterodimeric gamma-amino-butanoic acid subtype B (GABAB) receptors where either GABABR1a or GABABR1b are co-expressed with GABABR2 and the chimeric G-protein Galphaq-z5 in tsA cells [10].

 

References

  1. Heterodimerization of a functional GABAB receptor is mediated by parallel coiled-coil alpha-helices. Kammerer, R.A., Frank, S., Schulthess, T., Landwehr, R., Lustig, A., Engel, J. Biochemistry (1999) [Pubmed]
  2. Cloning of a novel G-protein-coupled receptor GPR 51 resembling GABAB receptors expressed predominantly in nervous tissues and mapped proximal to the hereditary sensory neuropathy type 1 locus on chromosome 9. Ng, G.Y., McDonald, T., Bonnert, T., Rigby, M., Heavens, R., Whiting, P., Chateauneuf, A., Coulombe, N., Kargman, S., Caskey, T., Evans, J., O'neill, G.P., Liu, Q. Genomics (1999) [Pubmed]
  3. Regulation by nicotine of gpr51 and ntrk2 expression in various rat brain regions. Sun, D., Huang, W., Hwang, Y.Y., Zhang, Y., Zhang, Q., Li, M.D. Neuropsychopharmacology (2007) [Pubmed]
  4. Evidence for glycosphingolipid modification of the type 1 IFN receptor. Ghislain, J., Lingwood, C.A., Fish, E.N. J. Immunol. (1994) [Pubmed]
  5. Molecular identification of the human GABABR2: cell surface expression and coupling to adenylyl cyclase in the absence of GABABR1. Martin, S.C., Russek, S.J., Farb, D.H. Mol. Cell. Neurosci. (1999) [Pubmed]
  6. Association between the gamma-aminobutyric acid type B receptor 1 and 2 gene polymorphisms and mesial temporal lobe epilepsy in a Han Chinese population. Wang, X., Sun, W., Zhu, X., Li, L., Wu, X., Lin, H., Zhu, S., Liu, A., Du, T., Liu, Y., Niu, N., Wang, Y., Liu, Y. Epilepsy. Res. (2008) [Pubmed]
  7. Neurochemical and molecular pharmacological aspects of the GABA(B) receptor. Kuriyama, K., Hirouchi, M., Kimura, H. Neurochem. Res. (2000) [Pubmed]
  8. Recent advances in GABAB receptors: from pharmacology to molecular biology. Ong, J., Kerr, D.I. Acta Pharmacol. Sin. (2000) [Pubmed]
  9. Comparative cellular distribution of GABAA and GABAB receptors in the human basal ganglia: immunohistochemical colocalization of the alpha 1 subunit of the GABAA receptor, and the GABABR1 and GABABR2 receptor subunits. Waldvogel, H.J., Billinton, A., White, J.H., Emson, P.C., Faull, R.L. J. Comp. Neurol. (2004) [Pubmed]
  10. Functional pharmacology of cloned heterodimeric GABAB receptors expressed in mammalian cells. Bräuner-Osborne, H., Krogsgaard-Larsen, P. Br. J. Pharmacol. (1999) [Pubmed]
 
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