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GABAB receptors and synaptic modulation

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Abstract

GABAB receptors modulate transmitter release and postsynaptic membrane potential at various types of central synapses. They function as heterodimers of two related seven-transmembrane domain receptor subunits. Trafficking, activation and signalling of GABAB receptors are regulated both by allosteric interactions between the subunits and by the binding of additional proteins. Recent studies have shed light on the roles of GABAB receptors in plasticity processes at excitatory synapses. This review summarizes our knowledge of the localization, structure and function of GABAB receptors in the central nervous system and their use as drug targets for neurological and psychiatric disorders.

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References

  • Balasubramanian S, Teissere JA, Raju DV, Hall RA (2004) Hetero-oligomerization between GABAA and GABAB receptors regulates GABAB receptor trafficking. J Biol Chem 279:18840–18850

    Article  PubMed  CAS  Google Scholar 

  • Becherer U, Rettig J (2006) Vesicle pools, docking, priming, and release. Cell Tissue Res (DOI 10.1007/s00441-006-0243-z; this issue)

  • Benke D, Honer M, Michel C, Bettler B, Möhler H (1999) Gamma-aminobutyric acid type B receptor splice variant proteins GBR1a and GBR1b are both associated with GBR2 in situ and display differential regional and subcellular distribution. J Biol Chem 274:27323–27330

    Article  PubMed  CAS  Google Scholar 

  • Bettler B, Tiao JY (2006) Molecular diversity, trafficking and subcellular localization of GABA(B) receptors. Pharmacol Ther 110:533–543

    Article  PubMed  CAS  Google Scholar 

  • Bettler B, Kaupmann K, Bowery N (1998) GABAB receptors: drugs meet clones. Curr Opin Neurobiol 8:345–350

    Article  PubMed  CAS  Google Scholar 

  • Bettler B, Kaupmann K, Mosbacher J, Gassmann M (2004) Molecular structure and physiological functions of GABA(B) receptors. Physiol Rev 84:835–867

    Article  PubMed  CAS  Google Scholar 

  • Billinton A, Ige AO, Bolam JP, White JH, Marshall FH, Emson PC (2001) Advances in the molecular understanding of GABA(B) receptors. Trends Neurosci 24:277–282

    Article  PubMed  CAS  Google Scholar 

  • Binet V, Brajon C, Le Corre L, Acher F, Pin JP, Prezeau 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 279:29085–29091

    Article  PubMed  CAS  Google Scholar 

  • Blein S, Ginham R, Uhrin D, Smith BO, Soares DC, Veltel S, McIlhinney RA, White JH, Barlow PN (2004) Structural analysis of the complement control protein (CCP) modules of GABA(B) receptor 1a: only one of the two CCP modules is compactly folded. J Biol Chem 279:48292–48306

    Article  PubMed  CAS  Google Scholar 

  • Bonanno G, Raiteri M (1993) Multiple GABAB receptors. Trends Pharmacol Sci 14:259–261

    Article  PubMed  CAS  Google Scholar 

  • Bonanno G, Fassio A, Schmid G, Severi P, Sala R, Raiteri M (1997) Pharmacologically distinct GABAB receptors that mediate inhibition of GABA and glutamate release in human neocortex. Br J Pharmacol 120:60–64

    Article  PubMed  CAS  Google Scholar 

  • Bouvier M (2001) Oligomerization of G-protein-coupled transmitter receptors. Nat Rev Neurosci 2:274–286

    Article  PubMed  CAS  Google Scholar 

  • Bowery NG (1993) GABAB receptor pharmacology. Annu Rev Pharmacol Toxicol 33:109–147

    PubMed  CAS  Google Scholar 

  • Bowery NG (2006) GABAB receptor: a site of therapeutic benefit. Curr Opin Pharmacol 6:37–43

    Article  PubMed  CAS  Google Scholar 

  • Bowery NG, Smart TG (2006) GABA and glycine as neurotransmitters: a brief history. Br J Pharmacol 147 Suppl 1:S109–119

    Article  PubMed  CAS  Google Scholar 

  • Bowery NG, Hill DR, Hudson AL, Doble A, Middlemiss DN, Shaw J, Turnbull M (1980) (-)Baclofen decreases neurotransmitter release in the mammalian CNS by an action at a novel GABA receptor. Nature 283:92–94

    Article  PubMed  CAS  Google Scholar 

  • Bowery NG, Bettler B, Froestl W, Gallagher JP, Marshall F, Raiteri M, Bonner TI, Enna SJ (2002) International Union of Pharmacology. XXXIII. Mammalian gamma-aminobutyric acid(B) receptors: structure and function. Pharmacol Rev 54:247–264

    Article  PubMed  CAS  Google Scholar 

  • Brock C, Boudier L, Maurel D, Blahos J, Pin JP (2005) Assembly-dependent surface targeting of the heterodimeric GABAB receptor is controlled by COPI but not 14-3-3. Mol Biol Cell 16:5572–5578

    Article  PubMed  CAS  Google Scholar 

  • Brody DL, Yue DT (2000) Relief of G-protein inhibition of calcium channels and short-term synaptic facilitation in cultured hippocampal neurons. J Neurosci 20:889–898

    PubMed  CAS  Google Scholar 

  • Brogden RN, Speight TM, Avery GS (1974) Baclofen: a preliminary report of its pharmacological properties and therapeutic efficacy in spasticity. Drugs 8:1–14

    Article  PubMed  CAS  Google Scholar 

  • Brown EM, MacLeod RJ (2001) Extracellular calcium sensing and extracellular calcium signaling. Physiol Rev 81:239–297

    PubMed  CAS  Google Scholar 

  • Calver AR, Robbins MJ, Cosio C, Rice SQ, Babbs AJ, Hirst WD, Boyfield I, Wood MD, Russell RB, Price GW, Couve A, Moss SJ, Pangalos MN (2001) The C-terminal domains of the GABA(b) receptor subunits mediate intracellular trafficking but are not required for receptor signaling. J Neurosci 21:1203–1210

    PubMed  CAS  Google Scholar 

  • Calver AR, Davies CH, Pangalos M (2002) GABA(B) receptors: from monogamy to promiscuity. Neurosignals 11:299–314

    Article  PubMed  CAS  Google Scholar 

  • Calver AR, Michalovich D, Testa TT, Robbins MJ, Jaillard C, Hill J, Szekeres PG, Charles KJ, Jourdain S, Holbrook JD, Boyfield I, Patel N, Medhurst AD, Pangalos MN (2003) Molecular cloning and characterisation of a novel GABAB-related G-protein coupled receptor. Brain Res Mol Brain Res 110:305–317

    Article  PubMed  CAS  Google Scholar 

  • Charles KJ, Deuchars J, Davies CH, Pangalos MN (2003) GABA B receptor subunit expression in glia. Mol Cell Neurosci 24:214–223

    Article  PubMed  CAS  Google Scholar 

  • Cousins MS, Roberts DC, Wit H de (2002) GABA(B) receptor agonists for the treatment of drug addiction: a review of recent findings. Drug Alcohol Depend 65:209–220

    Article  PubMed  CAS  Google Scholar 

  • Couve A, Filippov AK, Connolly CN, Bettler B, Brown DA, Moss SJ (1998) Intracellular retention of recombinant GABAB receptors. J Biol Chem 273:26361–26367

    Article  PubMed  CAS  Google Scholar 

  • Couve A, Kittler JT, Uren JM, Calver AR, Pangalos MN, Walsh FS, Moss SJ (2001) Association of GABA(B) receptors and members of the 14-3-3 family of signaling proteins. Mol Cell Neurosci 17:317–328

    Article  PubMed  CAS  Google Scholar 

  • Couve A, Thomas P, Calver AR, Hirst WD, Pangalos MN, Walsh FS, Smart TG, Moss SJ (2002) Cyclic AMP-dependent protein kinase phosphorylation facilitates GABA(B) receptor-effector coupling. Nat Neurosci 5:415–424

    PubMed  CAS  Google Scholar 

  • Couve A, Restituito S, Brandon JM, Charles KJ, Bawagan H, Freeman KB, Pangalos MN, Calver AR, Moss SJ (2004) Marlin-1, a novel RNA-binding protein associates with GABA receptors. J Biol Chem 279:13934–13943

    Article  PubMed  CAS  Google Scholar 

  • Cruz HG, Ivanova T, Lunn ML, Stoffel M, Slesinger PA, Lüscher C (2004) Bi-directional effects of GABA(B) receptor agonists on the mesolimbic dopamine system. Nat Neurosci 7:153–159

    Article  PubMed  CAS  Google Scholar 

  • Cryan JF, Kaupmann K (2005) Don’t worry ’B’ happy!: a role for GABA(B) receptors in anxiety and depression. Trends Pharmacol Sci 26:36–43

    Article  PubMed  CAS  Google Scholar 

  • Cryan JF, Kelly PH, Chaperon F, Gentsch C, Mombereau C, Lingenhoehl K, Froestl W, Bettler B, Kaupmann K, Spooren WP (2004) Behavioral characterization of the novel GABAB receptor-positive modulator GS39783 (N,N′-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine): anxiolytic-like activity without side effects associated with baclofen or benzodiazepines. J Pharmacol Exp Ther 310:952–963

    Article  PubMed  CAS  Google Scholar 

  • Cunningham MD, Enna SJ (1996) Evidence for pharmacologically distinct GABAB receptors associated with cAMP production in rat brain. Brain Res 720:220–224

    Article  PubMed  CAS  Google Scholar 

  • Davies CH, Starkey SJ, Pozza MF, Collingridge GL (1991) GABA autoreceptors regulate the induction of LTP. Nature 349:609–611

    Article  PubMed  CAS  Google Scholar 

  • Deriu D, Gassmann M, Firbank S, Ristig D, Lampert C, Mosbacher J, Froestl W, Kaupmann K, Bettler B, Grutter MG (2005) Determination of the minimal functional ligand-binding domain of the GABAB1b receptor. Biochem J 386:423–431

    Article  PubMed  CAS  Google Scholar 

  • Dittman JS, Regehr WG (1996) Contributions of calcium-dependent and calcium-independent mechanisms to presynaptic inhibition at a cerebellar synapse. J Neurosci 16:1623–1633

    PubMed  CAS  Google Scholar 

  • Dittman JS, Regehr WG (1997) Mechanism and kinetics of heterosynaptic depression at a cerebellar synapse. J Neurosci 17:9048–9059

    PubMed  CAS  Google Scholar 

  • Dityatev A, Schachner M (2006) The extracellular matrix and synapses. Cell Tissue Res (DOI 10.1007/s00441-006-0217-1; this issue)

  • Dulac C (2000) Sensory coding of pheromone signals in mammals. Curr Opin Neurobiol 10:511–518

    Article  PubMed  CAS  Google Scholar 

  • Dunlap K, Fischbach GD (1981) Neurotransmitters decrease the calcium conductance activated by depolarization of embryonic chick sensory neurones. J Physiol (Lond) 317:519–535

    CAS  Google Scholar 

  • Dutar P, Nicoll RA (1988) A physiological role for GABAB receptors in the central nervous system. Nature 332:156–158

    Article  PubMed  CAS  Google Scholar 

  • Duthey B, Caudron S, Perroy J, Bettler B, Fagni L, Pin JP, Prezeau L (2002) A single subunit (GB2) is required for G-protein activation by the heterodimeric GABA(B) receptor. J Biol Chem 277:3236–3241

    Article  PubMed  CAS  Google Scholar 

  • Fairfax BP, Pitcher JA, Scott MG, Calver AR, Pangalos MN, Moss SJ, Couve A (2004) Phosphorylation and chronic agonist treatment atypically modulate GABAB receptor cell surface stability. J Biol Chem 279:12565–12573

    Article  PubMed  CAS  Google Scholar 

  • Ferraguti F, Shigemoto R (2006) Metabotropic glutamate receptors. Cell Tissue Res (DOI 10.1007/s00441-006-0266-5; this issue)

  • Filippov AK, Couve A, Pangalos MN, Walsh FS, Brown DA, Moss SJ (2000) Heteromeric assembly of GABA(B)R1 and GABA(B)R2 receptor subunits inhibits Ca(2+) current in sympathetic neurons. J Neurosci 20:2867–2874

    PubMed  CAS  Google Scholar 

  • Fotiadis D, Liang Y, Filipek S, Saperstein DA, Engel A, Palczewski K (2003) Atomic-force microscopy: rhodopsin dimers in native disc membranes. Nature 421:127–128

    Article  PubMed  CAS  Google Scholar 

  • Fritschy JM, Meskenaite V, Weinmann O, Honer M, Benke D, Möhler H (1999) GABAB-receptor splice variants GB1a and GB1b in rat brain: developmental regulation, cellular distribution and extrasynaptic localization. Eur J Neurosci 11:761–768

    Article  PubMed  CAS  Google Scholar 

  • Fritschy JM, Sidler C, Parpan F, Gassmann M, Kaupmann K, Bettler B, Benke D (2004) Independent maturation of the GABA(B) receptor subunits GABA(B1) and GABA(B2) during postnatal development in rodent brain. J Comp Neurol 477:235–252

    Article  PubMed  CAS  Google Scholar 

  • Froestl W, Mickel SJ, Sprecher G von, Diel PJ, Hall RG, Maier L, Strub D, Melillo V, Baumann PA, Bernasconi R, et al (1995) Phosphinic acid analogues of GABA. 2. Selective, orally active GABAB antagonists. J Med Chem 38:3313–3331

    Article  PubMed  CAS  Google Scholar 

  • Froestl W, Gallagher M, Jenkins H, Madrid A, Melcher T, Teichman S, Mondadori CG, Pearlman R (2004) SGS742: the first GABA(B) receptor antagonist in clinical trials. Biochem Pharmacol 68:1479–1487

    Article  PubMed  CAS  Google Scholar 

  • Galvez T, Parmentier ML, Joly C, Malitschek B, Kaupmann K, Kuhn R, Bittiger H, Froestl W, Bettler B, Pin JP (1999) Mutagenesis and modeling of the GABAB receptor extracellular domain support a venus flytrap mechanism for ligand binding. J Biol Chem 274:13362–13369

    Article  PubMed  CAS  Google Scholar 

  • Galvez T, Prezeau L, Milioti G, Franek M, Joly C, Froestl W, Bettler B, Bertrand HO, Blahos J, Pin JP (2000a) Mapping the agonist-binding site of GABAB type 1 subunit sheds light on the activation process of GABAB receptors. J Biol Chem 275:41166–41174

    Article  PubMed  CAS  Google Scholar 

  • Galvez T, Urwyler S, Prezeau L, Mosbacher J, Joly C, Malitschek B, Heid J, Brabet I, Froestl W, Bettler B, Kaupmann K, Pin JP (2000b) 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 57:419–426

    PubMed  CAS  Google Scholar 

  • Galvez T, Duthey B, Kniazeff J, Blahos J, Rovelli G, Bettler B, Prezeau L, Pin JP (2001) Allosteric interactions between GB1 and GB2 subunits are required for optimal GABA(B) receptor function. EMBO J 20:2152–2159

    Article  PubMed  CAS  Google Scholar 

  • 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, Putten H van der, Mombereau C, Lecourtier L, Mosbacher J, Cryan JF, Fritschy JM, Luthi A, Kaupmann K, Bettler B (2004a) Redistribution of GABAB(1) protein and atypical GABAB responses in GABAB(2)-deficient mice. J Neurosci 24:6086–6097

    Article  PubMed  CAS  Google Scholar 

  • Gassmann M, Vigot R, Shaban H, Barbieri S, Brauner-Osborne H, Lüthi A, Cryan JF, Kaupmann K, Bettler B (2004b) Genetic dissection of GABAB receptor function in mice. Soc Neurosci Abstr 32:959.3

    Google Scholar 

  • Gassmann M, Haller C, Stoll Y, Aziz SA, Biermann B, Mosbacher J, Kaupmann K, Bettler B (2005) The RXR-type endoplasmic reticulum-retention/retrieval signal of GABAB(1) requires distant spacing from the membrane to function. Mol Pharmacol 68:137–144

    PubMed  CAS  Google Scholar 

  • George SR, O’Dowd BF, Lee SP (2002) G-protein-coupled receptor oligomerization and its potential for drug discovery. Nat Rev Drug Discov 1:808–820

    Article  PubMed  CAS  Google Scholar 

  • Gerber U, Gähwiler BH (1994) GABAB and adenosine receptors mediate enhancement of the K+ current, IAHP, by reducing adenylyl cyclase activity in rat CA3 hippocampal neurons. J Neurophysiol 72:2360–2367

    PubMed  CAS  Google Scholar 

  • Gonchar Y, Pang L, Malitschek B, Bettler B, Burkhalter A (2001) Subcellular localization of GABA(B) receptor subunits in rat visual cortex. J Comp Neurol 431:182–197

    Article  PubMed  CAS  Google Scholar 

  • Groc L, Choquet D (2006) AMPA and NMDA glutamate receptor trafficking: multiple roads for reaching and leaving the synapse. Cell Tissue Res (DOI 10.1007/s00441-006-00254-9; this issue)

  • Grünewald S, Schupp BJ, Ikeda SR, Kuner R, Steigerwald F, Kornau HC, Köhr G (2002) Importance of the gamma-aminobutyric acid(B) receptor C-termini for G-protein coupling. Mol Pharmacol 61:1070–1080

    Article  PubMed  Google Scholar 

  • Haller C, Casanova E, Muller M, Vacher CM, Vigot R, Doll T, Barbieri S, Gassmann M, Bettler B (2004) Floxed allele for conditional inactivation of the GABAB(1) gene. Genesis 40:125–130

    Article  PubMed  CAS  Google Scholar 

  • Harayama N, Shibuya I, Tanaka K, Kabashima N, Ueta Y, Yamashita H (1998) Inhibition of N- and P/Q-type calcium channels by postsynaptic GABAB receptor activation in rat supraoptic neurones. J Physiol (Lond) 509:371–383

    Article  CAS  Google Scholar 

  • Havlickova M, Prezeau L, Duthey B, Bettler B, Pin JP, Blahos J (2002) The intracellular loops of the GB2 subunit are crucial for G-protein coupling of the heteromeric gamma-aminobutyrate B receptor. Mol Pharmacol 62:343–350

    Article  PubMed  CAS  Google Scholar 

  • Helm KA, Haberman RP, Dean SL, Hoyt EC, Melcher T, Lund PK, Gallagher M (2005) GABAB receptor antagonist SGS742 improves spatial memory and reduces protein binding to the cAMP response element (CRE) in the hippocampus. Neuropharmacology 48:956–964

    Article  PubMed  CAS  Google Scholar 

  • Herman RM, D’Luzansky SC, Ippolito R (1992) Intrathecal baclofen suppresses central pain in patients with spinal lesions. A pilot study. Clin J Pain 8:338–345

    Article  PubMed  CAS  Google Scholar 

  • Hill DR (1985) GABAB receptor modulation of adenylate cyclase activity in rat brain slices. Br J Pharmacol 84:249–257

    PubMed  CAS  Google Scholar 

  • Hill DR, Bowery NG (1981) 3H-baclofen and 3H-GABA bind to bicuculline-insensitive GABA B sites in rat brain. Nature 290:149–152

    Article  PubMed  CAS  Google Scholar 

  • Hirono M, Yoshioka T, Konishi S (2001) GABA(B) receptor activation enhances mGluR-mediated responses at cerebellar excitatory synapses. Nat Neurosci 4:1207–1216

    Article  PubMed  CAS  Google Scholar 

  • Hosford DA, Clark S, Cao Z, Wilson WA Jr, Lin FH, Morrisett RA, Huin A (1992) The role of GABAB receptor activation in absence seizures of lethargic (l h/l h) mice. Science 257:398–401

    Article  PubMed  CAS  Google Scholar 

  • Huang CS, Shi SH, Ule J, Ruggiu M, Barker LA, Darnell RB, Jan YN, Jan LY (2005) Common molecular pathways mediate long-term potentiation of synaptic excitation and slow synaptic inhibition. Cell 123:105–118

    Article  PubMed  CAS  Google Scholar 

  • Ikeda SR (1996) Voltage-dependent modulation of N-type calcium channels by G-protein beta gamma subunits. Nature 380:255–258

    Article  PubMed  CAS  Google Scholar 

  • Isaacson JS (2000) Spillover in the spotlight. Curr Biol 10:R475–R477

    Article  PubMed  CAS  Google Scholar 

  • Isaacson JS, Solis JM, Nicoll RA (1993) Local and diffuse synaptic actions of GABA in the hippocampus. Neuron 10:165–175

    Article  PubMed  CAS  Google Scholar 

  • Jones KA, Borowsky B, Tamm JA, Craig DA, Durkin MM, Dai M, Yao WJ, Johnson M, Gunwaldsen C, Huang LY, Tang C, Shen Q, Salon JA, Morse K, Laz T, Smith KE, Nagarathnam D, Noble SA, Branchek TA, Gerald C (1998) GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2. Nature 396:674–679

    Article  PubMed  CAS  Google Scholar 

  • Kammerer RA, Frank S, Schulthess T, Landwehr R, Lustig A, Engel J (1999) Heterodimerization of a functional GABAB receptor is mediated by parallel coiled-coil alpha-helices. Biochemistry 38:13263–13269

    Article  PubMed  CAS  Google Scholar 

  • Kaupmann K, Huggel K, Heid J, Flor PJ, Bischoff S, Mickel SJ, McMaster G, Angst C, Bittiger H, Froestl W, Bettler B (1997) Expression cloning of GABA(B) receptors uncovers similarity to metabotropic glutamate receptors. Nature 386:239–246

    Article  PubMed  CAS  Google Scholar 

  • Kaupmann K, Malitschek B, Schuler V, Heid J, Froestl W, Beck P, Mosbacher J, Bischoff S, Kulik A, Shigemoto R, Karschin A, Bettler B (1998) GABA(B)-receptor subtypes assemble into functional heteromeric complexes. Nature 396:683–687

    Article  PubMed  CAS  Google Scholar 

  • Kerr DI, Ong J, Prager RH, Gynther BD, Curtis DR (1987) Phaclofen: a peripheral and central baclofen antagonist. Brain Res 405:150–154

    Article  PubMed  CAS  Google Scholar 

  • Kim E, Sheng M (2004) PDZ domain proteins of synapses. Nat Rev Neurosci 5:771–781

    Article  PubMed  CAS  Google Scholar 

  • Kitano J, Kimura K, Yamazaki Y, Soda T, Shigemoto R, Nakajima Y, Nakanishi S (2002) Tamalin, a PDZ domain-containing protein, links a protein complex formation of group 1 metabotropic glutamate receptors and the guanine nucleotide exchange factor cytohesins. J Neurosci 22:1280–1289

    PubMed  CAS  Google Scholar 

  • Kniazeff J, Galvez T, Labesse G, 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 22:7352–7361

    PubMed  CAS  Google Scholar 

  • Köhr G (2006) NMDA receptor function: Subunit composition versusspatial distribution. Cell Tissue Res (DOI 10.1007/s00441-006-0273-6; this issue)

  • Kofuji P, Davidson N, Lester HA (1995) Evidence that neuronal G-protein-gated inwardly rectifying K+ channels are activated by G beta gamma subunits and function as heteromultimers. Proc Natl Acad Sci USA 92:6542–6546

    Article  PubMed  CAS  Google Scholar 

  • Kornau HC, Seeburg PH, Kennedy MB (1997) Interaction of ion channels and receptors with PDZ domain proteins. Curr Opin Neurobiol 7:368–373

    Article  PubMed  CAS  Google Scholar 

  • Koyrakh L, Lujan R, Colon J, Karschin C, Kurachi Y, Karschin A, Wickman K (2005) Molecular and cellular diversity of neuronal G-protein-gated potassium channels. J Neurosci 25:11468–11478

    Article  PubMed  CAS  Google Scholar 

  • Kubo Y, Tateyama M (2005) Towards a view of functioning dimeric metabotropic receptors. Curr Opin Neurobiol 15:289–295

    Article  PubMed  CAS  Google Scholar 

  • Kuhn SA, Landeghem FK van, Zacharias R, Farber K, Rappert A, Pavlovic S, Hoffmann A, Nolte C, Kettenmann H (2004) Microglia express GABA(B) receptors to modulate interleukin release. Mol Cell Neurosci 25:312–322

    Article  PubMed  CAS  Google Scholar 

  • Kulik A, Nakadate K, Nyiri G, Notomi T, Malitschek B, Bettler B, Shigemoto R (2002) Distinct localization of GABA(B) receptors relative to synaptic sites in the rat cerebellum and ventrobasal thalamus. Eur J Neurosci 15:291–307

    Article  PubMed  Google Scholar 

  • Kulik A, Vida I, Lujan R, Haas CA, Lopez-Bendito G, Shigemoto R, Frotscher M (2003) Subcellular localization of metabotropic GABA(B) receptor subunits GABA(B1a/b) and GABA(B2) in the rat hippocampus. J Neurosci 23:11026–11035

    PubMed  CAS  Google Scholar 

  • Kulik A, Vida I, Fukazawa Y, Guetg N, Kasugai Y, Marker CL, Rigato F, Bettler B, Wickman K, Frotscher M, Shigemoto R (2006) Compartment-dependent colocalization of Kir3.2-containing K+ channels and GABAB receptors in hippocampal pyramidal cells. J Neurosci 26:4289–4297

    Article  PubMed  CAS  Google Scholar 

  • Kuner R, Köhr G, Grünewald S, Eisenhardt G, Bach A, Kornau HC (1999) Role of heteromer formation in GABAB receptor function. Science 283:74–77

    Article  PubMed  CAS  Google Scholar 

  • Kunishima N, Shimada Y, Tsuji Y, Sato T, Yamamoto M, Kumasaka T, Nakanishi S, Jingami H, Morikawa K (2000) Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor. Nature 407:971–977

    Article  PubMed  CAS  Google Scholar 

  • Lavine N, Ethier N, Oak JN, Pei L, Liu F, Trieu P, Rebois RV, Bouvier M, Hebert TE, Van Tol HH (2002) G protein-coupled receptors form stable complexes with inwardly rectifying potassium channels and adenylyl cyclase. J Biol Chem 277:46010–46019

    Article  PubMed  CAS  Google Scholar 

  • Liang Y, Fotiadis D, Filipek S, Saperstein DA, Palczewski K, Engel A (2003) Organization of the G protein-coupled receptors rhodopsin and opsin in native membranes. J Biol Chem 278:21655–21662

    Article  PubMed  CAS  Google Scholar 

  • Liu J, Maurel D, Etzol S, Brabet I, Ansanay H, Pin JP, Rondard P (2004) Molecular determinants involved in the allosteric control of agonist affinity in the GABAB receptor by the GABAB2 subunit. J Biol Chem 279:15824–15830

    Article  PubMed  CAS  Google Scholar 

  • Lopez-Bendito G, Shigemoto R, Kulik A, Paulsen O, Fairen A, Lujan R (2002) Expression and distribution of metabotropic GABA receptor subtypes GABABR1 and GABABR2 during rat neocortical development. Eur J Neurosci 15:1766–1778

    Article  PubMed  CAS  Google Scholar 

  • Lopez-Bendito G, Lujan R, Shigemoto R, Ganter P, Paulsen O, Molnar Z (2003) Blockade of GABA(B) receptors alters the tangential migration of cortical neurons. Cereb Cortex 13:932–942

    Article  PubMed  Google Scholar 

  • Lopez-Bendito G, Shigemoto R, Kulik A, Vida I, Fairen A, Lujan R (2004) Distribution of metabotropic GABA receptor subunits GABAB1a/b and GABAB2 in the rat hippocampus during prenatal and postnatal development. Hippocampus 14:836–848

    Article  PubMed  CAS  Google Scholar 

  • Lujan R, Shigemoto R (2006) Localization of metabotropic GABA receptor subunits GABA and GABA relative to synaptic sites in the rat developing cerebellum. Eur J Neurosci 23:1479–1490

    Article  PubMed  CAS  Google Scholar 

  • Lujan R, Shigemoto R, Kulik A, Juiz JM (2004) Localization of the GABAB receptor 1a/b subunit relative to glutamatergic synapses in the dorsal cochlear nucleus of the rat. J Comp Neurol 475:36–46

    Article  PubMed  CAS  Google Scholar 

  • Lüscher C, Jan LY, Stoffel M, Malenka RC, Nicoll RA (1997) G protein-coupled inwardly rectifying K+ channels (GIRKs) mediate postsynaptic but not presynaptic transmitter actions in hippocampal neurons. Neuron 19:687–695

    Article  PubMed  Google Scholar 

  • Malitschek B, Schweizer C, Keir M, Heid J, Froestl W, Mosbacher J, Kuhn R, Henley J, Joly C, Pin JP, Kaupmann K, Bettler B (1999) The N-terminal domain of gamma-aminobutyric acid(B) receptors is sufficient to specify agonist and antagonist binding. Mol Pharmacol 56:448–454

    PubMed  CAS  Google Scholar 

  • Marescaux C, Vergnes M, Liu Z, Depaulis A, Bernasconi R (1992) GABAB receptor involvement in the control of genetic absence seizures in rats. Epilepsy Res Suppl 9:131–139

    PubMed  CAS  Google Scholar 

  • Margeta-Mitrovic M, Mitrovic I, Riley RC, Jan LY, Basbaum AI (1999) Immunohistochemical localization of GABA(B) receptors in the rat central nervous system. J Comp Neurol 405:299–321

    Article  PubMed  CAS  Google Scholar 

  • Margeta-Mitrovic M, Jan YN, Jan LY (2000) A trafficking checkpoint controls GABA(B) receptor heterodimerization. Neuron 27:97–106

    Article  PubMed  CAS  Google Scholar 

  • Margeta-Mitrovic M, Jan YN, Jan LY (2001a) Function of GB1 and GB2 subunits in G protein coupling of GABA(B) receptors. Proc Natl Acad Sci USA 98:14649–14654

    Article  PubMed  CAS  Google Scholar 

  • Margeta-Mitrovic M, Jan YN, Jan LY (2001b) Ligand-induced signal transduction within heterodimeric GABA(B) receptor. Proc Natl Acad Sci USA 98:14643–14648

    Article  PubMed  CAS  Google Scholar 

  • Marshall FH (2005) Is the GABA B heterodimer a good drug target? J Mol Neurosci 26:169–176

    Article  PubMed  CAS  Google Scholar 

  • Marshall FH, Jones KA, Kaupmann K, Bettler B (1999) GABAB receptors—the first 7TM heterodimers. Trends Pharmacol Sci 20:396–399

    Article  PubMed  CAS  Google Scholar 

  • Martin SC, Russek SJ, 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 13:180–191

    Article  PubMed  CAS  Google Scholar 

  • Michelsen K, Yuan H, Schwappach B (2005) Hide and run. Arginine-based endoplasmic-reticulum-sorting motifs in the assembly of heteromultimeric membrane proteins. EMBO Rep 6:717–722

    Article  PubMed  CAS  Google Scholar 

  • Milligan G, White JH (2001) Protein-protein interactions at G-protein-coupled receptors. Trends Pharmacol Sci 22:513–518

    Article  PubMed  CAS  Google Scholar 

  • Mintz IM, Bean BP (1993) GABAB receptor inhibition of P-type Ca2+ channels in central neurons. Neuron 10:889–898

    Article  PubMed  CAS  Google Scholar 

  • Misgeld U, Bijak M, Jarolimek W (1995) A physiological role for GABAB receptors and the effects of baclofen in the mammalian central nervous system. Prog Neurobiol 46:423–462

    Article  PubMed  CAS  Google Scholar 

  • Möhler H (2006) GABAA receptor diversity and pharmacology . Cell Tissue Res (DOI 10.1007/s00441-006-0284-3; this issue)

  • Möhler H, Fritschy JM (1999) GABAB receptors make it to the top—as dimers. Trends Pharmacol Sci 20:87–89

    Article  PubMed  Google Scholar 

  • Mombereau C, Kaupmann K, Froestl W, Sansig G, Putten H van der, Cryan JF (2004a) Genetic and pharmacological evidence of a role for GABA(B) receptors in the modulation of anxiety- and antidepressant-like behavior. Neuropsychopharmacology 29:1050–1062

    Article  PubMed  CAS  Google Scholar 

  • Mombereau C, Kaupmann K, Putten H van der, Cryan JF (2004b) Altered response to benzodiazepine anxiolytics in mice lacking GABA B(1) receptors. Eur J Pharmacol 497:119–120

    Article  PubMed  CAS  Google Scholar 

  • Mombereau C, Kaupmann K, Gassmann M, Bettler B, Putten H van der, Cryan JF (2005) Altered anxiety and depression-related behaviour in mice lacking GABAB(2) receptor subunits. Neuroreport 16:307–310

    Article  PubMed  CAS  Google Scholar 

  • Mondadori C, Jaekel J, Preiswerk G (1993) CGP 36742: the first orally active GABAB blocker improves the cognitive performance of mice, rats, and rhesus monkeys. Behav Neural Biol 60:62–68

    Article  PubMed  CAS  Google Scholar 

  • Mott DD, Lewis DV (1991) Facilitation of the induction of long-term potentiation by GABAB receptors. Science 252:1718–1720

    Article  PubMed  CAS  Google Scholar 

  • Mutneja M, Berton F, Suen KF, Lüscher C, Slesinger PA (2005) Endogenous RGS proteins enhance acute desensitization of GABA(B) receptor-activated GIRK currents in HEK-293T cells. Pflugers Arch 450:61–73

    Article  PubMed  CAS  Google Scholar 

  • Nehring RB, Horikawa HP, El Far O, Kneussel M, Brandstatter JH, Stamm S, Wischmeyer E, Betz H, Karschin A (2000) The metabotropic GABAB receptor directly interacts with the activating transcription factor 4. J Biol Chem 275:35185–35191

    Article  PubMed  CAS  Google Scholar 

  • Newberry NR, Nicoll RA (1984) Direct hyperpolarizing action of baclofen on hippocampal pyramidal cells. Nature 308:450–452

    Article  PubMed  CAS  Google Scholar 

  • Newberry NR, Nicoll RA (1985) Comparison of the action of baclofen with gamma-aminobutyric acid on rat hippocampal pyramidal cells in vitro. J Physiol (Lond) 360:161–185

    CAS  Google Scholar 

  • Ng GY, Clark J, Coulombe N, Ethier N, Hebert TE, Sullivan R, Kargman S, Chateauneuf A, Tsukamoto N, McDonald T, Whiting P, Mezey E, Johnson MP, Liu Q, Kolakowski LF Jr, Evans JF, Bonner TI, O’Neill GP (1999) Identification of a GABAB receptor subunit, gb2, required for functional GABAB receptor activity. J Biol Chem 274:7607–7610

    Article  PubMed  CAS  Google Scholar 

  • Otis TS, De Koninck Y, Mody I (1993) Characterization of synaptically elicited GABAB responses using patch-clamp recordings in rat hippocampal slices. J Physiol (Lond) 463:391–407

    CAS  Google Scholar 

  • Otmakhova NA, Lisman JE (2004) Contribution of Ih and GABAB to synaptically induced afterhyperpolarizations in CA1: a brake on the NMDA response. J Neurophysiol 92:2027–2039

    Article  PubMed  CAS  Google Scholar 

  • Pagano A, Rovelli G, Mosbacher J, Lohmann T, Duthey B, Stauffer D, Ristig D, Schuler V, Meigel I, Lampert C, Stein T, Prezeau L, Blahos J, Pin J, Froestl W, Kuhn R, Heid J, Kaupmann K, Bettler B (2001) C-terminal interaction is essential for surface trafficking but not for heteromeric assembly of GABA(b) receptors. J Neurosci 21:1189–1202

    PubMed  CAS  Google Scholar 

  • Panzanelli P, Lopez-Bendito G, Lujan R, Sassoe-Pognetto M (2004) Localization and developmental expression of GABA(B) receptors in the rat olfactory bulb. J Neurocytol 33:87–99

    Article  PubMed  CAS  Google Scholar 

  • Perez-Garci E, Gassmann M, Bettler B, Larkum ME (2006) The GABA(B1b) isoform mediates long-lasting inhibition of dendritic Ca(2+) spikes in layer 5 somatosensory pyramidal neurons. Neuron 50:603–616

    Article  PubMed  CAS  Google Scholar 

  • Perroy J, Adam L, Qanbar R, Chenier S, Bouvier M (2003) Phosphorylation-independent desensitization of GABA(B) receptor by GRK4. EMBO J 22:3816–3824

    Article  PubMed  CAS  Google Scholar 

  • Pfrieger FW, Gottmann K, Lux HD (1994) Kinetics of GABAB receptor-mediated inhibition of calcium currents and excitatory synaptic transmission in hippocampal neurons in vitro. Neuron 12:97–107

    Article  PubMed  CAS  Google Scholar 

  • Pin JP, Parmentier ML, Prezeau L (2001) Positive allosteric modulators for gamma-aminobutyric acid(B) receptors open new routes for the development of drugs targeting family 3 G-protein-coupled receptors. Mol Pharmacol 60:881–884

    PubMed  CAS  Google Scholar 

  • Pin JP, Kniazeff J, Liu J, Binet V, Goudet C, Rondard P, Prezeau L (2005) Allosteric functioning of dimeric class C G-protein-coupled receptors. FEBS J 272:2947–2955

    Article  PubMed  CAS  Google Scholar 

  • Poncer JC, McKinney RA, Gähwiler BH, Thompson SM (2000) Differential control of GABA release at synapses from distinct interneurons in rat hippocampus. J Physiol (Lond) 528:123–130

    Article  CAS  Google Scholar 

  • Pranzatelli MR (1992) The neurobiology of the opsoclonus-myoclonus syndrome. Clin Neuropharmacol 15:186–228

    Article  PubMed  CAS  Google Scholar 

  • Priest CA, Puche AC (2004) GABAB receptor expression and function in olfactory receptor neuron axon growth. J Neurobiol 60:154–165

    Article  PubMed  CAS  Google Scholar 

  • Prosser HM, Gill CH, Hirst WD, Grau E, Robbins M, Calver A, Soffin EM, Farmer CE, Lanneau C, Gray J, Schenck E, Warmerdam BS, Clapham C, Reavill C, Rogers DC, Stean T, Upton N, Humphreys K, Randall A, Geppert M, Davies CH, Pangalos MN (2001) Epileptogenesis and enhanced prepulse inhibition in GABA(B1)-deficient mice. Mol Cell Neurosci 17:1059–1070

    Article  PubMed  CAS  Google Scholar 

  • Queva C, Bremner-Danielsen M, Edlund A, Ekstrand AJ, Elg S, Erickson S, Johansson T, Lehmann A, Mattsson JP (2003) Effects of GABA agonists on body temperature regulation in GABA(B(1))-/- mice. Br J Pharmacol 140:315–322

    Article  PubMed  CAS  Google Scholar 

  • Restituito S, Couve A, Bawagan H, Jourdain S, Pangalos MN, Calver AR, Freeman KB, Moss SJ (2005) Multiple motifs regulate the trafficking of GABA(B) receptors at distinct checkpoints within the secretory pathway. Mol Cell Neurosci 28:747–756

    Article  PubMed  CAS  Google Scholar 

  • Robbins MJ, Calver AR, Filippov AK, Hirst WD, Russell RB, Wood MD, Nasir S, Couve A, Brown DA, Moss SJ, Pangalos MN (2001) GABA(B2) is essential for G-protein coupling of the GABA(B) receptor heterodimer. J Neurosci 21:8043–8052

    PubMed  CAS  Google Scholar 

  • Romano C, Yang WL, O’Malley KL (1996) Metabotropic glutamate receptor 5 is a disulfide-linked dimer. J Biol Chem 271:28612–28616

    Article  PubMed  CAS  Google Scholar 

  • Saghatelyan AK, Snapyan M, Gorissen S, Meigel I, Mosbacher J, Kaupmann K, Bettler B, Kornilov AV, Nifantiev NE, Sakanyan V, Schachner M, Dityatev A (2003) Recognition molecule associated carbohydrate inhibits postsynaptic GABA(B) receptors: a mechanism for homeostatic regulation of GABA release in perisomatic synapses. Mol Cell Neurosci 24:271–282

    Article  PubMed  CAS  Google Scholar 

  • Sakaba T, Neher E (2003) Direct modulation of synaptic vesicle priming by GABA(B) receptor activation at a glutamatergic synapse. Nature 424:775–778

    Article  PubMed  CAS  Google Scholar 

  • Sauter K, Grampp T, Fritschy JM, Kaupmann K, Bettler B, Möhler H, Benke D (2005) Subtype-selective interaction with the transcription factor CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) regulates cell surface expression of GABA(B) receptors. J Biol Chem 280:33566–33572

    Article  PubMed  CAS  Google Scholar 

  • Scanziani M (2000) GABA spillover activates postsynaptic GABA(B) receptors to control rhythmic hippocampal activity. Neuron 25:673–681

    Article  PubMed  CAS  Google Scholar 

  • Schneggenburger R, Forsythe ID (2006) Calyx of held. Cell Tissue Res (DOI 10.1007/s00441-006-0272-7; this issue)

  • Scholz KP, Miller RJ (1991) GABAB receptor-mediated inhibition of Ca2+ currents and synaptic transmission in cultured rat hippocampal neurones. J Physiol (Lond) 444:669–686

    CAS  Google Scholar 

  • Schuler V, Lüscher C, Blanchet C, Klix N, Sansig G, Klebs K, Schmutz M, Heid J, Gentry C, Urban L, Fox A, Spooren W, Jaton AL, Vigouret J, Pozza M, Kelly PH, Mosbacher J, Froestl W, Kaslin E, Korn R, Bischoff S, Kaupmann K, Putten H van der, Bettler B (2001) Epilepsy, hyperalgesia, impaired memory, and loss of pre- and postsynaptic GABA(B) responses in mice lacking GABA(B(1)). Neuron 31:47–58

    Article  PubMed  CAS  Google Scholar 

  • Scott K (2004) The sweet and the bitter of mammalian taste. Curr Opin Neurobiol 14:423–427

    Article  PubMed  CAS  Google Scholar 

  • Simonds WF (1999) G protein regulation of adenylate cyclase. Trends Pharmacol Sci 20:66–73

    Article  PubMed  CAS  Google Scholar 

  • Slattery DA, Markou A, Froestl W, Cryan JF (2005) The GABAB receptor-positive modulator GS39783 and the GABAB receptor agonist baclofen attenuate the reward-facilitating effects of cocaine: intracranial self-stimulation studies in the rat. Neuropsychopharmacology 30:2065–2072

    Article  PubMed  CAS  Google Scholar 

  • Smith MA, Yancey DL, Morgan D, Liu Y, Froestl W, Roberts DC (2004) Effects of positive allosteric modulators of the GABAB receptor on cocaine self-administration in rats. Psychopharmacology (Berl) 173:105–111

    Article  CAS  Google Scholar 

  • Steiger JL, Bandyopadhyay S, Farb DH, 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 24:6115–6126

    Article  PubMed  CAS  Google Scholar 

  • Stevens CF (2004) Presynaptic function. Curr Opin Neurobiol 14:341–345

    Article  PubMed  CAS  Google Scholar 

  • Tabata T, Aiba A, Kano M (2002) Extracellular calcium controls the dynamic range of neuronal metabotropic glutamate receptor responses. Mol Cell Neurosci 20:56–68

    Article  PubMed  CAS  Google Scholar 

  • Tabata T, Araishi K, Hashimoto K, Hashimotodani Y, Putten H van der, Bettler B, Kano M (2004) Ca2+ activity at GABAB receptors constitutively promotes metabotropic glutamate signaling in the absence of GABA. Proc Natl Acad Sci USA 101:16952–16957

    Article  PubMed  CAS  Google Scholar 

  • Taira T, Tanikawa T, Kawamura H, Iseki H, Takakura K (1994) Spinal intrathecal baclofen suppresses central pain after a stroke. J Neurol Neurosurg Psychiatry 57:381–382

    Article  PubMed  CAS  Google Scholar 

  • Takahashi T, Kajikawa Y, Tsujimoto T (1998) G-protein-coupled modulation of presynaptic calcium currents and transmitter release by a GABAB receptor. J Neurosci 18:3138–3146

    PubMed  CAS  Google Scholar 

  • Thompson SM, Gähwiler BH (1992) Comparison of the actions of baclofen at pre- and postsynaptic receptors in the rat hippocampus in vitro. J Physiol (Lond) 451:329–345

    CAS  Google Scholar 

  • Thuault SJ, Brown JT, Sheardown SA, Jourdain S, Fairfax B, Spencer JP, Restituito S, Nation JH, Topps S, Medhurst AD, Randall AD, Couve A, Moss SJ, Collingridge GL, Pangalos MN, Davies CH, Calver AR (2004) The GABA(B2) subunit is critical for the trafficking and function of native GABA(B) receptors. Biochem Pharmacol 68:1655–1666

    Article  PubMed  CAS  Google Scholar 

  • Ule J, Jensen KB, Ruggiu M, Mele A, Ule A, Darnell RB (2003) CLIP identifies Nova-regulated RNA networks in the brain. Science 302:1212–1215

    Article  PubMed  CAS  Google Scholar 

  • Ule J, Ule A, Spencer J, Williams A, Hu JS, Cline M, Wang H, Clark T, Fraser C, Ruggiu M, Zeeberg BR, Kane D, Weinstein JN, Blume J, Darnell RB (2005) Nova regulates brain-specific splicing to shape the synapse. Nat Genet 37:844–852

    Article  PubMed  CAS  Google Scholar 

  • Urwyler S, Mosbacher J, Lingenhoehl K, Heid J, Hofstetter K, Froestl W, Bettler B, 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 60:963–971

    PubMed  CAS  Google Scholar 

  • Urwyler S, Pozza MF, Lingenhoehl K, Mosbacher J, Lampert C, Froestl W, Koller M, 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 307:322–330

    Article  PubMed  CAS  Google Scholar 

  • Vergnes M, Boehrer A, Simler S, Bernasconi R, Marescaux C (1997) Opposite effects of GABAB receptor antagonists on absences and convulsive seizures. Eur J Pharmacol 332:245–255

    Article  PubMed  CAS  Google Scholar 

  • Vernon E, Meyer G, Pickard L, Dev K, Molnar E, Collingridge GL, Henley JM (2001) GABA(B) receptors couple directly to the transcription factor ATF4. Mol Cell Neurosci 17:637–645

    Article  PubMed  CAS  Google Scholar 

  • Vigot R, Barbieri S, Brauner-Osborne H, Turecek R, Shigemoto R, Zhang YP, Lujan R, Jacobson LH, Biermann B, Fritschy JM, Vacher CM, Muller M, Sansig G, Guetg N, Cryan JF, Kaupmann K, Gassmann M, Oertner TG, Bettler B (2006) Differential compartmentalization and distinct functions of GABA(B) receptor variants. Neuron 50:589–601

    Article  PubMed  CAS  Google Scholar 

  • Vogt KE, Nicoll RA (1999) Glutamate and gamma-aminobutyric acid mediate a heterosynaptic depression at mossy fiber synapses in the hippocampus. Proc Natl Acad Sci USA 96:1118–1122

    Article  PubMed  CAS  Google Scholar 

  • White JH, Wise A, Main MJ, Green A, Fraser NJ, Disney GH, Barnes AA, Emson P, Foord SM, Marshall FH (1998) Heterodimerization is required for the formation of a functional GABA(B) receptor. Nature 396:679–682

    Article  PubMed  CAS  Google Scholar 

  • White JH, McIllhinney RA, Wise A, Ciruela F, Chan WY, Emson PC, Billinton A, Marshall FH (2000) The GABAB receptor interacts directly with the related transcription factors CREB2 and ATFx. Proc Natl Acad Sci USA 97:13967–13972

    Article  PubMed  CAS  Google Scholar 

  • White JH, Ginham R, Pontier S, Wise A, Blein S, Barlow P, Bouvier M, McIlhinney RA (2002) The heterodimeric GABAB receptor and associated proteins. FENS Abstr 1:062.061

    Google Scholar 

  • Wise A, Green A, Main MJ, Wilson R, Fraser N, Marshall FH (1999) Calcium sensing properties of the GABA(B) receptor. Neuropharmacology 38:1647–1656

    Article  PubMed  CAS  Google Scholar 

  • Wu LG, Saggau P (1997) Presynaptic inhibition of elicited neurotransmitter release. Trends Neurosci 20:204–212

    Article  PubMed  CAS  Google Scholar 

  • Wu LG, Borst JG, Sakmann B (1998) R-type Ca2+ currents evoke transmitter release at a rat central synapse. Proc Natl Acad Sci USA 95:4720–4725

    Article  PubMed  CAS  Google Scholar 

  • Xi ZX, Stein EA (1999) Baclofen inhibits heroin self-administration behavior and mesolimbic dopamine release. J Pharmacol Exp Ther 290:1369–1374

    PubMed  CAS  Google Scholar 

  • Yang YY, Yin GL, Darnell RB (1998) The neuronal RNA-binding protein Nova-2 is implicated as the autoantigen targeted in POMA patients with dementia. Proc Natl Acad Sci USA 95:13254–13259

    Article  PubMed  CAS  Google Scholar 

  • Yuan H, Michelsen K, Schwappach B (2003) 14-3-3 Dimers probe the assembly status of multimeric membrane proteins. Curr Biol 13:638–646

    Article  PubMed  CAS  Google Scholar 

  • Zerangue N, Schwappach B, Jan YN, Jan LY (1999) A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels. Neuron 22:537–548

    Article  PubMed  CAS  Google Scholar 

  • Zilberter Y, Kaiser KM, Sakmann B (1999) Dendritic GABA release depresses excitatory transmission between layer 2/3 pyramidal and bitufted neurons in rat neocortex. Neuron 24:979–988

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

I thank D. Zunner, C. Deschermeier, T. Bartoi and G. Köhr for critically reading the manuscript.

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    Hans-Christian Kornau

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Kornau, HC. GABAB receptors and synaptic modulation. Cell Tissue Res 326, 517–533 (2006). https://doi.org/10.1007/s00441-006-0264-7

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