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The GABAB Receptor

From Cloning to Knockout Mice

  • Chapter
Molecular Neuropharmacology

Abstract

γ-Aminobutyric acid (GABA) is the prevalent inhibitory neurotransmitter in the brain. It exerts it action through ligand-gated Cl- channel (GABAA and GABAC receptors) and G protein coupled receptors (GPCR) that inhibit adenylate cyclase (GABAB receptors) (1–3). GABAB receptors were first identified in the early 1980s on the basis of pharmacological responses to the agonist baclofen (Fig. 1) and insensitivity to the GABAA antagonist bicuculline (4,5), but resisted cloning until the late 1990s. Several groups made unsuccessful attempts to isolate the receptor protein by affinity chromatography (6,7) or to expression clone the receptor in Xenopus oocytes using electrophysiology (8–10). Eventually, medicinal chemistry efforts produced the highly potent radiolabeled GABAB antagonists [125I]CGP64213 and [125I]CGP71872 (Fig. 1) and provided the necessary tools for expression cloning (11). After screening of two million rat brain cDNA clones using a radioligand binding assay the first GABAB(l) receptor clone was isolated (12). Cloning of the GABAB(l) cDNA was a major milestone in the field as it paved the way for studies on the structure, function, and pharmacology of GABAB receptors at the molecular level.

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Authors
  1. Bernhard Bettler
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  2. Hans Bräuner-Osborne
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Editors and Affiliations

  1. Department of Pharmacology, The Danish University of Pharmaceutical Sciences, Copenhagen, Denmark

    Arne Schousboe PhD, DSc

  2. Department of Medical Chemistry, The Danish University of Pharmaceutical Sciences, Copenhagen, Denmark

    Hans Bräuner-Osborne PhD, DSc

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Bettler, B., Bräuner-Osborne, H. (2004). The GABAB Receptor. In: Schousboe, A., Bräuner-Osborne, H. (eds) Molecular Neuropharmacology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-672-0_7

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  • DOI: https://doi.org/10.1007/978-1-59259-672-0_7

  • Publisher Name: Humana Press, Totowa, NJ

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