Agonist-induced desensitization and endocytosis of heterodimeric GABA B receptors in CHO-K1 cells

Javier González-Maeso, Alan Wise, Andrew Green, Jennifer A. Koenig

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24 Scopus citations


γ-Aminobutyric acid B (GABAB) receptor is the first discovered G protein-coupled receptor that requires two subunits, GB1 and GB2, to form a functional receptor. Whereas the molecular and functional characteristics of GABAB receptors have been recently extensively studied, the mechanisms underlying receptor desensitization and endocytosis are still poorly understood. We have investigated the effect of continuous agonist exposure on the human GABAB receptor functional response and redistribution when expressed in Chinese hamster ovary (CHO-K1) cells. The wild-type GABAB receptor-mediated inhibition of the adenylate cyclase activity appeared desensitized after 2 h in the presence of GABA (100 μM). Fusion proteins were generated by attachment of cyan fluorescent protein (CFP) and yellow fluorescent protein (YFP) to GB1 and GB2, respectively, and confocal microscopy experiments in intact living cells semi-stably expressing the constructs were performed. Incubation of co-expressing CFP-GB1 and YFP-GB2 cells in the presence of GABA (100 μM) for 2 h induced a profound receptor internalization, and CFP-GB1 and YFP-GB2 appeared co-localized in the endosome (labelled with Cy3-transferrin). The internalization was blocked by a selective GABAB receptor antagonist. These results represent the first clear visualization of agonist-induced internalization of the unique heterodimeric GABAB receptor.

Original languageEnglish
Pages (from-to)15-23
Number of pages9
JournalEuropean Journal of Pharmacology
Issue number1
StatePublished - 14 Nov 2003


  • Desensitization
  • Endocytosis
  • GABA receptor
  • Green fluorescent protein (GFP)
  • Receptor dimerization


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