Distribution and Localization of the GABAB Receptor
Distribution and Localization of the GABAB Receptor
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DOI：
10.1007/978-3-319-46044-4_5
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发表时间：
2016-01-01
期刊：
影响因子：
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通讯作者：
Gessa, Gian Luigi
中科院分区：
文献类型：
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作者：
Castelli, M. Paola;Gessa, Gian Luigi
The functional GABA(B) receptors (GABA(B) Rs) are formed by obligate heteromers composed of two principal subunits named GABA(B1) and GABA(B2). In Drosophila melanogaster three GABA(B) subunits have been identifi ed: GB1, GB2, and GB3. The GB1 and GB2 subunits need to be coexpressed in Xenopus oocytes or in mammalian cell lines to produce functional GABAB(R)s. A subfamily of potassium channel tetramerization domain-containing (KCTD8, 12, 12b, and 16) proteins that are constituents of native GABA(B)Rs were recently identifi ed. KCTDs show a temporal and spatial distribution pattern that may contribute to the heterogeneity of native GABA(B)Rs and their pharmacological properties.Of several isoforms of the GABA(B)1 subunit identifi ed to date, the most abundant in the brain are the isoforms 1a and 1b; they are coexpressed with the subunit GABA(B2) and their expression differs across brain and neuronal populations. GABA(B1a) localizes to glutamatergic terminals and is necessary for hetero-receptor function. Both isoforms 1a and 1b are detected in dendrites, but only GABA(B1b) in spine heads. Electron microscopy studies show that, in the central nervous system (CNS), GABA(B1) and GABA(B2) are both pre-and postsynaptic, but mostly localize to postsynaptic sites. The GABA(B1(a/b)) and GABA(B2) subunits show an overlapping pattern of distribution throughout the CNS with certain exceptions (i.e., caudate-putamen and cerebellum). GABA(B) Rs are also detected in Schwann cells, in several peripheral tissues, and in nonneuronal cells (cardiomyocytes and airway smooth muscle). The widespread distribution of GABA(B) Rs in the CNS and the periphery refl ects their physiological, pathophysiological, and pharmacological relevance.
