IUPHAR/BPS Guide to Pharmacology CITE
https://doi.org/10.2218/gtopdb/F26/2019.4

GABAB receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database



Bernhard Bettler1, Norman G. Bowery2, John F. Cryan3, Sam J. Enna4, David H. Farb5, Wolfgang Foestl6, Klemens Kaupmann6 and Jean-Philippe Pin7
  1. University of Basel, Switzerland
  2. GlaxoSmithKline, Italy
  3. University College Cork, Ireland
  4. University of Kansas Medical Center, USA
  5. Boston University, USA
  6. Novartis Institutes for Biomedical Research, Switzerland
  7. Université de Montpellier, France


Abstract

Functional GABAB receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on GABAB receptors [11, 72]) are formed from the heterodimerization of two similar 7TM subunits termed GABAB1 and GABAB2 [11, 71, 28, 72, 85]. GABAB receptors are widespread in the CNS and regulate both pre- and postsynaptic activity. The GABAB1 subunit, when expressed alone, binds both antagonists and agonists, but the affinity of the latter is generally 10-100-fold less than for the native receptor. Co-expression of GABAB1 and GABAB2 subunits allows transport of GABAB1 to the cell surface and generates a functional receptor that can couple to signal transduction pathways such as high-voltage-activated Ca2+ channels (Cav2.1, Cav2.2), or inwardly rectifying potassium channels (Kir3) [12, 11, 5]. The GABAB1 subunit harbours the GABA (orthosteric)-binding site within an extracellular domain (ECD) venus flytrap module (VTM), whereas the GABAB2 subunit mediates G protein-coupled signalling [11, 71, 40, 39]. The two subunits interact by direct allosteric coupling [63], such that GABAB2 increases the affinity of GABAB1 for agonists and reciprocally GABAB1 facilitates the coupling of GABAB2 to G proteins [71, 54, 39]. GABAB1 and GABAB2 subunits assemble in a 1:1 stoichiometry by means of a coiled-coil interaction between α-helices within their carboxy-termini that masks an endoplasmic reticulum retention motif (RXRR) within the GABAB1 subunit but other domains of the proteins also contribute to their heteromerization [5, 71, 15]. Recent evidence indicates that higher order assemblies of GABAB receptor comprising dimers of heterodimers occur in recombinant expression systems and in vivo and that such complexes exhibit negative functional cooperativity between heterodimers [70, 22]. Adding further complexity, KCTD (potassium channel tetramerization proteins) 8, 12, 12b and 16 associate as tetramers with the carboxy terminus of the GABAB2 subunit to impart altered signalling kinetics and agonist potency to the receptor complex [84, 3, 79] and are reviewed by [73]. The molecular complexity of GABAB receptors is further increased through association with trafficking and effector proteins [Schwenk et al., 2016, Nature Neuroscience 19(2): 233-42] and reviewed by [69]. Four isoforms of the human GABAB1 subunit have been cloned. The predominant GABAB1a and GABAB1b isoforms, which are most prevalent in neonatal and adult brain tissue respectively, differ in their ECD sequences as a result of the use of alternative transcription initiation sites. GABAB1a-containing heterodimers localise to distal axons and mediate inhibition of glutamate release in the CA3-CA1 terminals, and GABA release onto the layer 5 pyramidal neurons, whereas GABAB1b-containing receptors occur within dendritic spines and mediate slow postsynaptic inhibition [75, 89]. Only the 1a and 1b variants are identified as components of native receptors [11]. Additional GABAB1 subunit isoforms have been described in rodents and humans [55] and reviewed by [5].

Contents

This is a citation summary for GABAB receptors in the Guide to Pharmacology database (GtoPdb). It exists purely as an adjunct to the database to facilitate the recognition of citations to and from the database by citation analyzers. Readers will almost certainly want to visit the relevant sections of the database which are given here under database links.

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Database links

GABAB receptors
http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=26
Introduction to GABAB receptors
http://www.guidetopharmacology.org/GRAC/FamilyIntroductionForward?familyId=26
    Receptors
        Complexes
            GABAB receptor
            http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=242
        Receptors and Subunits
            GABAB1
            http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=240
            GABAB2
            http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=241
        Accessory Proteins
            KCTD16
            http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1920
            KCTD8
            http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1917
            kctd12b
            http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1919
            KCTD12
            http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1918

References

  1. Adams CL and Lawrence AJ. (2007) CGP7930: a positive allosteric modulator of the GABAB receptor. CNS Drug Rev 13: 308-16 [PMID:17894647]
  2. AstraZeneca. Lesogaberan (AZD3355).
  3. Bartoi T, Rigbolt KT, Du D, Köhr G, Blagoev B and Kornau HC. (2010) GABAB receptor constituents revealed by tandem affinity purification from transgenic mice. J. Biol. Chem. 285: 20625-33 [PMID:20406808]
  4. Belley M, Sullivan R, Reeves A, Evans J, O'Neill G and Ng GY. (1999) Synthesis of the nanomolar photoaffinity GABA(B) receptor ligand CGP 71872 reveals diversity in the tissue distribution of GABA(B) receptor forms. Bioorg. Med. Chem. 7: 2697-704 [PMID:10658574]
  5. Bettler B, Kaupmann K, Mosbacher J and Gassmann M. (2004) Molecular structure and physiological functions of GABA(B) receptors. Physiol. Rev. 84: 835-67 [PMID:15269338]
  6. Biermann B, Ivankova-Susankova K, Bradaia A, Abdel Aziz S, Besseyrias V, Kapfhammer JP, Missler M, Gassmann M and Bettler B. (2010) The Sushi domains of GABAB receptors function as axonal targeting signals. J. Neurosci. 30: 1385-94 [PMID:20107064]
  7. Binet V, Brajon C, Le Corre L, Acher F, Pin JP and Prézeau L. (2004) The heptahelical domain of GABA(B2) is activated directly by CGP7930, a positive allosteric modulator of the GABA(B) receptor. J. Biol. Chem. 279: 29085-91 [PMID:15126507]
  8. Bolser DC, Blythin DJ, Chapman RW, Egan RW, Hey JA, Rizzo C, Kuo SC and Kreutner W. (1995) The pharmacology of SCH 50911: a novel, orally-active GABA-beta receptor antagonist. J. Pharmacol. Exp. Ther. 274: 1393-8 [PMID:7562513]
  9. Bonanno G and Raiteri M. (1993) gamma-Aminobutyric acid (GABA) autoreceptors in rat cerebral cortex and spinal cord represent pharmacologically distinct subtypes of the GABAB receptor. J. Pharmacol. Exp. Ther. 265: 765-70 [PMID:8388458]
  10. Bowery NG. (1993) GABAB receptor pharmacology. Annu. Rev. Pharmacol. Toxicol. 33: 109-47 [PMID:8388192]
  11. Bowery NG, Bettler B, Froestl W, Gallagher JP, Marshall F, Raiteri M, Bonner TI and Enna SJ. (2002) International Union of Pharmacology. XXXIII. Mammalian gamma-aminobutyric acid(B) receptors: structure and function. Pharmacol. Rev. 54: 247-64 [PMID:12037141]
  12. Bowery NG and Enna SJ. (2000) gamma-aminobutyric acid(B) receptors: first of the functional metabotropic heterodimers. J. Pharmacol. Exp. Ther. 292: 2-7 [PMID:10604925]
  13. Bowery NG, Hudson AL and Price GW. (1987) GABAA and GABAB receptor site distribution in the rat central nervous system. Neuroscience 20: 365-83 [PMID:3035421]
  14. Brown JT, Gill CH, Farmer CE, Lanneau C, Randall AD, Pangalos MN, Collingridge GL and Davies CH. (2003) Mechanisms contributing to the exacerbated epileptiform activity in hippocampal slices of GABAB1 receptor subunit knockout mice. Epilepsy Res. 57: 121-36 [PMID:15013053]
  15. Burmakina S, Geng Y, Chen Y and Fan QR. (2014) Heterodimeric coiled-coil interactions of human GABAB receptor. Proc. Natl. Acad. Sci. U.S.A. 111: 6958-63 [PMID:24778228]
  16. Calver AR, Medhurst AD, Robbins MJ, Charles KJ, Evans ML, Harrison DC, Stammers M, Hughes SA, Hervieu G and Couve A et al.. (2000) The expression of GABA(B1) and GABA(B2) receptor subunits in the cNS differs from that in peripheral tissues. Neuroscience 100: 155-70 [PMID:10996466]
  17. Charles KJ, Evans ML, Robbins MJ, Calver AR, Leslie RA and Pangalos MN. (2001) Comparative immunohistochemical localisation of GABA(B1a), GABA(B1b) andGABA(B2) subunits in rat brain, spinal cord and dorsal root ganglion. Neuroscience 106: 447-467 [PMID:11591450]
  18. Chen LH, Sun B, Zhang Y, Xu TJ, Xia ZX, Liu JF and Nan FJ. (2014) Discovery of a Negative Allosteric Modulator of GABAB Receptors. ACS Med Chem Lett 5: 742-7 [PMID:25050158]
  19. Chu DC, Albin RL, Young AB and Penney JB. (1990) Distribution and kinetics of GABAB binding sites in rat central nervous system: a quantitative autoradiographic study. Neuroscience 34: 341-57 [PMID:2159128]
  20. Clark JA, Mezey E, Lam AS and Bonner TI. (1998) Functional expression and distribution of GB2 a second GABABreceptor. Soc. Neurosci. Abstr. 24: 795-798
  21. Clark JA, Mezey E, Lam AS and Bonner TI. (2000) Distribution of the GABA(B) receptor subunit gb2 in rat CNS. Brain Res. 860: 41-52 [PMID:10727622]
  22. Comps-Agrar L, Kniazeff J, Nørskov-Lauritsen L, Maurel D, Gassmann M, Gregor N, Prézeau L, Bettler B, Durroux T and Trinquet E et al.. (2011) The oligomeric state sets GABA(B) receptor signalling efficacy. EMBO J. 30: 2336-49 [PMID:21552208]
  23. Crunelli V and Leresche N. (1991) A role for GABAB receptors in excitation and inhibition of thalamocortical cells. Trends Neurosci. 14: 16-21 [PMID:1709527]
  24. Dupuis DS, Relkovic D, Lhuillier L, Mosbacher J and Kaupmann K. (2006) Point mutations in the transmembrane region of GABAB2 facilitate activation by the positive modulator N,N'-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine (GS39783) in the absence of the GABAB1 subunit. Mol. Pharmacol. 70: 2027-36 [PMID:16966477]
  25. Durkin MM, Gunwaldsen CA, Borowsky B, Jones KA and Branchek TA. (1999) An in situ hybridization study of the distribution of the GABA(B2) protein mRNAin the rat CNS. Brain Res Mol Brain Res. 71: 185-200 [PMID:10521573]
  26. Dutar P and Nicoll RA. (1988) A physiological role for GABAB receptors in the central nervous system. Nature 332: 156-8 [PMID:2831457]
  27. Duthey B, Caudron S, Perroy J, Bettler B, Fagni L, Pin JP and Prézeau L. (2002) A single subunit (GB2) is required for G-protein activation by the heterodimeric GABA(B) receptor. J. Biol. Chem. 277: 3236-41 [PMID:11711539]
  28. Emson PC. (2007) GABA(B) receptors: structure and function. Prog. Brain Res. 160: 43-57 [PMID:17499108]
  29. Enna SJ and Bowery NG. (2004) GABA(B) receptor alterations as indicators of physiological and pharmacological function. Biochem. Pharmacol. 68: 1541-8 [PMID:15451397]
  30. Fritschy JM, Meskenaite V, Weinmann O, Honer M, Benke D and Mohler H. (1999) GABAB-receptor splice variants GB1a and GB1b in rat brain: developmental regulation, cellular distribution and extrasynaptic localization. Eur. J. Neurosci. 11: 761-8 [PMID:10103070]
  31. Froestl W. (2011) An historical perspective on GABAergic drugs. Future Med Chem 3: 163-75 [PMID:21428811]
  32. Froestl W and Mickel SJ. (1997) Chemistry of GABAB modulators. In The GABA Receptors Edited by Enna SJ, Bowery NG: Humana Press: 271-296 [ISBN: 0896034585]
  33. Froestl W, Mickel SJ, von Sprecher G, Diel PJ, Hall RG, Maier L, Strub D, Melillo V, Baumann PA and Bernasconi R et al.. (1995) Phosphinic acid analogues of GABA. 2. Selective, orally active GABAB antagonists. J. Med. Chem. 38: 3313-31 [PMID:7650685]
  34. Galvez T, Duthey B, Kniazeff J, Blahos J, Rovelli G, Bettler B, Prézeau L and Pin JP. (2001) Allosteric interactions between GB1 and GB2 subunits are required for optimal GABA(B) receptor function. EMBO J. 20: 2152-9 [PMID:11331581]
  35. Galvez T, Urwyler S, Prézeau L, Mosbacher J, Joly C, Malitschek B, Heid J, Brabet I, Froestl W and Bettler B et al.. (2000) Ca(2+) requirement for high-affinity gamma-aminobutyric acid (GABA) binding at GABA(B) receptors: involvement of serine 269 of the GABA(B)R1 subunit. Mol. Pharmacol. 57: 419-26 [PMID:10692480]
  36. Gassmann M and Bettler B. (2012) Regulation of neuronal GABA(B) receptor functions by subunit composition. Nat. Rev. Neurosci. 13: 380-94 [PMID:22595784]
  37. Gassmann M, Shaban H, Vigot R, Sansig G, Haller C, Barbieri S, Humeau Y, Schuler V, Muller M, Kinzel B, Klebs K, Schmutz M, Froestl W, Heid J, Kelly PH, Gentry C, Jaton AL, van der Putten H, Mombereau C, Lecourtier L, Mosbacher J, Cryan JF, Fritschy JM, Luthi A, Kaupmann K and Bettler B. (2004) Redistribution of GABAB(1) protein and atypical GABAB responses in GABAB(2)-deficient mice. J Neurosci 24: 6086-6097 [PMID:15240800]
  38. Gemignani A, Paudice P, Bonanno G and Raiteri M. (1994) Pharmacological discrimination between gamma-aminobutyric acid type B receptors regulating cholecystokinin and somatostatin release from rat neocortex synaptosomes. Mol. Pharmacol. 46: 558-62 [PMID:7935338]
  39. Geng Y, Bush M, Mosyak L, Wang F and Fan QR. (2013) Structural mechanism of ligand activation in human GABA(B) receptor. Nature 504: 254-9 [PMID:24305054]
  40. Geng Y, Xiong D, Mosyak L, Malito DL, Kniazeff J, Chen Y, Burmakina S, Quick M, Bush M and Javitch JA et al.. (2012) Structure and functional interaction of the extracellular domain of human GABA(B) receptor GBR2. Nat. Neurosci. 15: 970-8 [PMID:22660477]
  41. Goei VL, Choi J, Ahn J, Bowlus CL, Raha-Chowdhury R and Gruen JR. (1998) Human gamma-aminobutyric acid B receptor gene: complementary DNA cloning, expression, chromosomal location, and genomic organization. Biol. Psychiatry 44: 659-66 [PMID:9798068]
  42. Grifa A, Totaro A, Rommens JM, Carella M, Roetto A, Borgato L, Zelante L and Gasparini P. (1998) GABA (gamma-amino-butyric acid) neurotransmission: identification and fine mapping of the human GABAB receptor gene. Biochem. Biophys. Res. Commun. 250: 240-5 [PMID:9753614]
  43. Hill DR. (1985) GABAB receptor modulation of adenylate cyclase activity in rat brain slices. Br. J. Pharmacol. 84: 249-57 [PMID:2579700]
  44. Hill DR and Bowery NG. (1981) 3H-baclofen and 3H-GABA bind to bicuculline-insensitive GABA B sites in rat brain. Nature 290: 149-52 [PMID:6259535]
  45. Hirst WD, Babbs AJ, Green A, Minton JA, Shaw TE, Wise A, Rice SQ, Pangalos MN and Price GW. (2003) Pharmacological characterisation of a cell line expressing GABA B1b and GABA B2 receptor subunits. Biochem. Pharmacol. 65: 1103-13 [PMID:12663046]
  46. Isomoto S, Kaibara M, Sakurai-Yamashita Y, Nagayama Y, Uezono Y, Yano K and Taniyama K. (1998) Cloning and tissue distribution of novel splice variants of the rat GABAB receptor. Biochem. Biophys. Res. Commun. 253: 10-5 [PMID:9875211]
  47. Jones KA, Borowsky B, Tamm JA, Craig DA, Durkin MM, Dai M, Yao WJ, Johnson M, Gunwaldsen C and Huang LY et al.. (1998) GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2. Nature 396: 674-9 [PMID:9872315]
  48. Kaupmann K, Huggel K, Heid J, Flor PJ, Bischoff S, Mickel SJ, McMaster G, Angst C, Bittiger H and Froestl W et al.. (1997) Expression cloning of GABA(B) receptors uncovers similarity to metabotropic glutamate receptors. Nature 386: 239-46 [PMID:9069281]
  49. Kaupmann K, Malitschek B, Schuler V, Heid J, Froestl W, Beck P, Mosbacher J, Bischoff S, Kulik A and Shigemoto R et al.. (1998) GABA(B)-receptor subtypes assemble into functional heteromeric complexes. Nature 396: 683-7 [PMID:9872317]
  50. Keir MJ, Barakat MJ, Dev KK, Bittiger H, Bettler B and Henley JM. (1999) Characterisation and partial purification of the GABA(B) receptor from the rat cerebellum using the novel antagonist [3H]CGP 62349. Brain Res. Mol. Brain Res. 71: 279-89 [PMID:10521582]
  51. Kniazeff J, Galvez T, Labesse G and Pin JP. (2002) No ligand binding in the GB2 subunit of the GABA(B) receptor is required for activation and allosteric interaction between the subunits. J. Neurosci. 22: 7352-61 [PMID:12196556]
  52. Kniazeff J, Saintot PP, Goudet C, Liu J, Charnet A, Guillon G and Pin JP. (2004) Locking the dimeric GABA(B) G-protein-coupled receptor in its active state. J. Neurosci. 24: 370-7 [PMID:14724235]
  53. Knight AR and Bowery NG. (1996) The pharmacology of adenylyl cyclase modulation by GABAB receptors in rat brain slices. Neuropharmacology 35: 703-12 [PMID:8887979]
  54. Kubo Y and Tateyama M. (2005) Towards a view of functioning dimeric metabotropic receptors. Curr. Opin. Neurobiol. 15: 289-95 [PMID:15922585]
  55. Lee C, Mayfield RD and Harris RA. (2010) Intron 4 containing novel GABAB1 isoforms impair GABAB receptor function. PLoS ONE 5: e14044 [PMID:21124972]
  56. Margeta-Mitrovic M, Jan YN and Jan LY. (2001) Function of GB1 and GB2 subunits in G protein coupling of GABA(B) receptors. Proc. Natl. Acad. Sci. U.S.A. 98: 14649-54 [PMID:11724956]
  57. Margeta-Mitrovic M, Jan YN and Jan LY. (2000) A trafficking checkpoint controls GABA(B) receptor heterodimerization. Neuron 27: 97-106 [PMID:10939334]
  58. Margeta-Mitrovic M, Mitrovic I, Riley RC, Jan LY and Basbaum AI. (1999) Immunohistochemical localization of GABA(B) receptors in the rat central nervous system. J. Comp. Neurol. 405: 299-321 [PMID:10076927]
  59. Martin SC, Russek SJ and Farb DH. (2001) Human GABA(B)R genomic structure: evidence for splice variants in GABA(B)R1 but not GABA(B)R2. Gene 278: 63-79 [PMID:11707323]
  60. Martin SC, Russek SJ and Farb DH. (1999) Molecular identification of the human GABABR2: cell surface expression and coupling to adenylyl cyclase in the absence of GABABR1. Mol. Cell. Neurosci. 13: 180-91 [PMID:10328880]
  61. Martin SC, Steiger JL, Gravielle MC, Lyons HR, Russek SJ and Farb DH. (2004) Differential expression of gamma-aminobutyric acid type B receptor subunit mRNAs in the developing nervous system and receptor coupling to adenylyl cyclase in embryonic neurons. J Comp Neurol 473: 16-29 [PMID:15067715]
  62. Massone S, Vassallo I, Fiorino G, Castelnuovo M, Barbieri F, Borghi R, Tabaton M, Robello M, Gatta E and Russo C et al.. (2011) 17A, a novel non-coding RNA, regulates GABA B alternative splicing and signaling in response to inflammatory stimuli and in Alzheimer disease. Neurobiol. Dis. 41: 308-17 [PMID:20888417]
  63. Monnier C, Tu H, Bourrier E, Vol C, Lamarque L, Trinquet E, Pin JP and Rondard P. (2011) Trans-activation between 7TM domains: implication in heterodimeric GABAB receptor activation. EMBO J. 30: 32-42 [PMID:21063387]
  64. Newberry NR and Nicoll RA. (1984) Direct hyperpolarizing action of baclofen on hippocampal pyramidal cells. Nature 308: 450-2 [PMID:6709051]
  65. Ng GY, McDonald T, Bonnert T, Rigby M, Heavens R, Whiting P, Chateauneuf A, Coulombe N, Kargman S and Caskey T et al.. (1999) 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. Genomics 56: 288-95 [PMID:10087195]
  66. Patel S, Naeem S, Kesingland A, Froestl W, Capogna M, Urban L and Fox A. (2001) The effects of GABA(B) agonists and gabapentin on mechanical hyperalgesia in models of neuropathic and inflammatory pain in the rat. Pain 90: 217-26 [PMID:11207393]
  67. Peters HC, Kämmer G, Volz A, Kaupmann K, Ziegler A, Bettler B, Epplen JT, Sander T and Riess O. (1998) Mapping, genomic structure, and polymorphisms of the human GABABR1 receptor gene: evaluation of its involvement in idiopathic generalized epilepsy. Neurogenetics 2: 47-54 [PMID:9933300]
  68. Pfaff T, Malitschek B, Kaupmann K, Prézeau L, Pin JP, Bettler B and Karschin A. (1999) Alternative splicing generates a novel isoform of the rat metabotropic GABA(B)R1 receptor. Eur. J. Neurosci. 11: 2874-82 [PMID:10457184]
  69. Pin JP and Bettler B. (2016) Organization and functions of mGlu and GABAB receptor complexes. Nature 540: 60-68 [PMID:27905440]
  70. Pin JP, Comps-Agrar L, Maurel D, Monnier C, Rives ML, Trinquet E, Kniazeff J, Rondard P and Prézeau L. (2009) G-protein-coupled receptor oligomers: two or more for what? Lessons from mGlu and GABAB receptors. J. Physiol. (Lond.) 587: 5337-44 [PMID:19723778]
  71. Pin JP, Kniazeff J, Binet V, Liu J, Maurel D, Galvez T, Duthey B, Havlickova M, Blahos J and Prézeau L et al.. (2004) Activation mechanism of the heterodimeric GABA(B) receptor. Biochem. Pharmacol. 68: 1565-72 [PMID:15451400]
  72. Pin JP, Neubig R, Bouvier M, Devi L, Filizola M, Javitch JA, Lohse MJ, Milligan G, Palczewski K and Parmentier M et al.. (2007) International Union of Basic and Clinical Pharmacology. LXVII. Recommendations for the recognition and nomenclature of G protein-coupled receptor heteromultimers. Pharmacol. Rev. 59: 5-13 [PMID:17329545]
  73. Pinard A, Seddik R and Bettler B. (2010) GABAB receptors: physiological functions and mechanisms of diversity. Adv. Pharmacol. 58: 231-55 [PMID:20655485]
  74. Prosser HM, Gill CH, Hirst WD, Grau E, Robbins M, Calver A, Soffin EM, Farmer CE, Lanneau C and Gray J et al.. (2001) Epileptogenesis and enhanced prepulse inhibition in GABA(B1)-deficient mice. Mol. Cell. Neurosci. 17: 1059-70 [PMID:11414794]
  75. Pérez-Garci E, Gassmann M, Bettler B and Larkum ME. (2006) The GABAB1b isoform mediates long-lasting inhibition of dendritic Ca2+ spikes in layer 5 somatosensory pyramidal neurons. Neuron 50: 603-16 [PMID:16701210]
  76. Quéva C, Bremner-Danielsen M, Edlund A, Ekstrand AJ, Elg S, Erickson S, Johansson T, Lehmann A and Mattsson JP. (2003) Effects of GABA agonists on body temperature regulation in GABA(B(1))-/- mice. Br. J. Pharmacol. 140: 315-22 [PMID:12970075]
  77. Schuler V, Lüscher C, Blanchet C, Klix N, Sansig G, Klebs K, Schmutz M, Heid J, Gentry C and Urban L et al.. (2001) Epilepsy, hyperalgesia, impaired memory, and loss of pre- and postsynaptic GABA(B) responses in mice lacking GABA(B(1)). Neuron 31: 47-58 [PMID:11498050]
  78. Schwarz DA, Barry G, Eliasof SD, Petroski RE, Conlon PJ and Maki RA. (2000) Characterization of gamma-aminobutyric acid receptor GABAB(1e), a GABAB(1) splice variant encoding a truncated receptor. J. Biol. Chem. 275: 32174-81 [PMID:10906333]
  79. Schwenk J, Metz M, Zolles G, Turecek R, Fritzius T, Bildl W, Tarusawa E, Kulik A, Unger A and Ivankova K et al.. (2010) Native GABA(B) receptors are heteromultimers with a family of auxiliary subunits. Nature 465: 231-5 [PMID:20400944]
  80. Sloviter RS, Ali-Akbarian L, Elliott RC, Bowery BJ and Bowery NG. (1999) Localization of GABAB(R1) receptors in the rat hippocampus by immunocytochemistry and high resolution autoradiography, with specific reference to its localization in identified hippocampal interneuron subpopulations. Neuropharmacology 38: 1707-1721 [PMID:10587087]
  81. Steiger JL, Bandyopadhyay S, Farb DH and Russek SJ. (2004) cAMP response element-binding protein, activating transcription factor-4, and upstream stimulatory factor differentially control hippocampal GABABR1a and GABABR1b subunit gene expression through alternative promoters. J. Neurosci. 24: 6115-26 [PMID:15240803]
  82. Sullivan R, Chateauneuf A, Coulombe N, Kolakowski Jr LF, Johnson MP, Hebert TE, Ethier N, Belley M, Metters K and Abramovitz M et al.. (2000) Coexpression of full-length gamma-aminobutyric acid(B) (GABA(B)) receptors with truncated receptors and metabotropic glutamate receptor 4 supports the GABA(B) heterodimer as the functional receptor. J. Pharmacol. Exp. Ther. 293: 460-7 [PMID:10773016]
  83. Sun D, Huang W, Hwang YY, Zhang Y, Zhang Q and Li MD. (2007) Regulation by nicotine of Gpr51 and Ntrk2 expression in various rat brain regions. Neuropsychopharmacology 32: 110-6 [PMID:16794563]
  84. Turecek R, Schwenk J, Fritzius T, Ivankova K, Zolles G, Adelfinger L, Jacquier V, Besseyrias V, Gassmann M and Schulte U et al.. (2014) Auxiliary GABAB receptor subunits uncouple G protein βγ subunits from effector channels to induce desensitization. Neuron 82: 1032-44 [PMID:24836506]
  85. Ulrich D and Bettler B. (2007) GABA(B) receptors: synaptic functions and mechanisms of diversity. Curr. Opin. Neurobiol. 17: 298-303 [PMID:17433877]
  86. Urwyler S, Mosbacher J, Lingenhoehl K, Heid J, Hofstetter K, Froestl W, Bettler B and Kaupmann K. (2001) Positive allosteric modulation of native and recombinant gamma-aminobutyric acid(B) receptors by 2,6-Di-tert-butyl-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930) and its aldehyde analog CGP13501. Mol. Pharmacol. 60: 963-71 [PMID:11641424]
  87. Urwyler S, Pozza MF, Lingenhoehl K, Mosbacher J, Lampert C, Froestl W, Koller M and Kaupmann K. (2003) N,N'-Dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine (GS39783) and structurally related compounds: novel allosteric enhancers of gamma-aminobutyric acidB receptor function. J. Pharmacol. Exp. Ther. 307: 322-30 [PMID:12954816]
  88. Vacher CM, Gassmann M, Desrayaud S, Challet E, Bradaia A, Hoyer D, Waldmeier P, Kaupmann K, Pévet P and Bettler B. (2006) Hyperdopaminergia and altered locomotor activity in GABAB1-deficient mice. J. Neurochem. 97: 979-91 [PMID:16606363]
  89. Vigot R, Barbieri S, Bräuner-Osborne H, Turecek R, Shigemoto R, Zhang YP, Luján R, Jacobson LH, Biermann B and Fritschy JM et al.. (2006) Differential compartmentalization and distinct functions of GABAB receptor variants. Neuron 50: 589-601 [PMID:16701209]
  90. Vlachou S, Guery S, Froestl W, Banerjee D, Benedict J, Finn MG and Markou A. (2011) Repeated administration of the GABAB receptor positive modulator BHF177 decreased nicotine self-administration, and acute administration decreased cue-induced reinstatement of nicotine seeking in rats. Psychopharmacology (Berl.) 215: 117-28 [PMID:21181127]
  91. Voisin DL and Nagy F. (2001) Sustained L-type calcium currents in dissociated deep dorsal horn neurons of the rat: characteristics and modulation. Neuroscience 102: 461-72 [PMID:11166132]
  92. Wei K, Eubanks JH, Francis J, Jia Z and Snead 3rd OC. (2001) Cloning and tissue distribution of a novel isoform of the rat GABA(B)R1 receptor subunit. Neuroreport 12: 833-7 [PMID:11277592]
  93. Wei K, Jia Z, Wang YT, Yang J, Liu CC and Snead 3rd OC. (2001) Cloning and characterization of a novel variant of rat GABA(B)R1 with a truncated C-terminus. Brain Res. Mol. Brain Res. 89: 103-10 [PMID:11311980]
  94. White JH, Wise A, Main MJ, Green A, Fraser NJ, Disney GH, Barnes AA, Emson P, Foord SM and Marshall FH. (1998) Heterodimerization is required for the formation of a functional GABA(B) receptor. Nature 396: 679-82 [PMID:9872316]
  95. Wood MD, Murkitt KL, Rice SQ, Testa T, Punia PK, Stammers M, Jenkins O, Elshourbagy NA, Shabon U and Taylor SJ et al.. (2000) The human GABA(B1b) and GABA(B2) heterodimeric recombinant receptor shows low sensitivity to phaclofen and saclofen. Br. J. Pharmacol. 131: 1050-4 [PMID:11082110]
  96. Xu J and Wojcik WJ. (1986) Gamma aminobutyric acid B receptor-mediated inhibition of adenylate cyclase in cultured cerebellar granule cells: blockade by islet-activating protein. J. Pharmacol. Exp. Ther. 239: 568-73 [PMID:2430096]