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Distribution and Localization of the GABAB Receptor

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GABAB Receptor

Part of the book series: The Receptors ((REC,volume 29))

Abstract

The functional GABAB receptors (GABABRs) are formed by obligate heteromers composed of two principal subunits named GABAB1 and GABAB2. In Drosophila melanogaster three GABAB subunits have been identified: GB1, GB2, and GB3. The GB1 and GB2 subunits need to be coexpressed in Xenopus oocytes or in mammalian cell lines to produce functional GABABRs. A subfamily of potassium channel tetramerization domain-containing (KCTD8, 12, 12b, and 16) proteins that are constituents of native GABABRs were recently identified. KCTDs show a temporal and spatial distribution pattern that may contribute to the heterogeneity of native GABABRs and their pharmacological properties.

Of several isoforms of the GABAB1 subunit identified to date, the most abundant in the brain are the isoforms 1a and 1b; they are coexpressed with the subunit GABAB2 and their expression differs across brain and neuronal populations. GABAB1a localizes to glutamatergic terminals and is necessary for hetero-receptor function. Both isoforms 1a and 1b are detected in dendrites, but only GABAB1b in spine heads. Electron microscopy studies show that, in the central nervous system (CNS), GABAB1 and GABAB2 are both pre- and postsynaptic, but mostly localize to postsynaptic sites. The GABAB1(a/b) and GABAB2 subunits show an overlapping pattern of distribution throughout the CNS with certain exceptions (i.e., caudate–putamen and cerebellum). GABABRs are also detected in Schwann cells, in several peripheral tissues, and in nonneuronal cells (cardiomyocytes and airway smooth muscle). The widespread distribution of GABABRs in the CNS and the periphery reflects their physiological, pathophysiological, and pharmacological relevance.

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  1. Division of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, SS 554, km. 4,500, 09042, Monserrato (CA), Italy

    M. Paola Castelli & Gian Luigi Gessa

  2. Center of Excellence “Neurobiology of Addiction”, University of Cagliari, 09042, Monserrato (CA), Italy

    M. Paola Castelli & Gian Luigi Gessa

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Correspondence to M. Paola Castelli .

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  1. Neuroscience Institute, National Research Council of Italy Neuroscience Institute, Cagliari, Italy

    Giancarlo Colombo

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Castelli, M.P., Gessa, G.L. (2016). Distribution and Localization of the GABAB Receptor. In: Colombo, G. (eds) GABAB Receptor. The Receptors, vol 29. Humana Press, Cham. https://doi.org/10.1007/978-3-319-46044-4_5

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