| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Pharmazentrum, Department of Clinical-Biological Sciences, Institute of Physiology, University of Basel, and Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland
GABAB receptors are broadly expressed in the nervous system and have been implicated in a wide variety of neurological and psychiatric disorders. The cloning of the first GABAB receptor cDNAs in 1997 revived interest in these receptors and their potential as therapeutic targets. With the availability of molecular tools, rapid progress was made in our understanding of the GABAB system. This led to the surprising discovery that GABAB receptors need to assemble from distinct subunits to function and provided exciting new insights into the structure of G protein-coupled receptors (GPCRs) in general. As a consequence of this discovery, it is now widely accepted that GPCRs can exist as heterodimers. The cloning of GABAB receptors allowed some important questions in the field to be answered. It is now clear that molecular studies do not support the existence of pharmacologically distinct GABAB receptors, as predicted by work on native receptors. Advances were also made in clarifying the relationship between GABAB receptors and the receptors for 
-hydroxybutyrate, an emerging drug of abuse. There are now the first indications linking GABAB receptor polymorphisms to epilepsy. Significantly, the cloning of GABAB receptors enabled identification of the first allosteric GABAB receptor compounds, which is expected to broaden the spectrum of therapeutic applications. Here we review current concepts on the molecular composition and function of GABAB receptors and discuss ongoing drug-discovery efforts.
This article has been cited by other articles:
|
|
 |
|
  A. Lehmann, M. Antonsson, A. A. Holmberg, L. A. Blackshaw, L. Branden, H. Brauner-Osborne, B. Christiansen, J. Dent, T. Elebring, B.-M. Jacobson, et al. (R)-(3-Amino-2-fluoropropyl) Phosphinic Acid (AZD3355), a Novel GABAB Receptor Agonist, Inhibits Transient Lower Esophageal Sphincter Relaxation through a Peripheral Mode of Action J. Pharmacol. Exp. Ther., November 1, 2009; 331(2): 504 - 512. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. A. Ramirez, R. L. Vidal, J. A. Tello, K. J. Vargas, S. Kindler, S. Hartel, and A. Couve Dendritic Assembly of Heteromeric {gamma}-Aminobutyric Acid Type B Receptor Subunits in Hippocampal Neurons J. Biol. Chem., May 8, 2009; 284(19): 13077 - 13085. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Matsuki, M. Nomiyama, H. Takahira, N. Hirashima, S. Kunita, S. Takahashi, K.-i. Yagami, T. S. Kilduff, B. Bettler, M. Yanagisawa, et al. Selective loss of GABAB receptors in orexin-producing neurons results in disrupted sleep/wakefulness architecture PNAS, March 17, 2009; 106(11): 4459 - 4464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Guetg, R. Seddik, R. Vigot, R. Turecek, M. Gassmann, K. E. Vogt, H. Brauner-Osborne, R. Shigemoto, O. Kretz, M. Frotscher, et al. The GABAB1a Isoform Mediates Heterosynaptic Depression at Hippocampal Mossy Fiber Synapses J. Neurosci., February 4, 2009; 29(5): 1414 - 1423. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ellefsen, K.-O. Stenslokken, C. E. Fagernes, T. A. Kristensen, and G. E. Nilsson Expression of genes involved in GABAergic neurotransmission in anoxic crucian carp brain (Carassius carassius) Physiol Genomics, January 8, 2009; 36(2): 61 - 68. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Rotte, J. Witte, W. Blenau, O. Baumann, and B. Walz Source, topography and excitatory effects of GABAergic innervation in cockroach salivary glands J. Exp. Biol., January 1, 2009; 212(1): 126 - 136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Wilkins, X. Li, and T. G. Smart Tracking Cell Surface GABAB Receptors Using an {alpha}-Bungarotoxin Tag J. Biol. Chem., December 12, 2008; 283(50): 34745 - 34752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Y. Tiao, A. Bradaia, B. Biermann, K. Kaupmann, M. Metz, C. Haller, A. G. Rolink, E. Pless, P. N. Barlow, M. Gassmann, et al. The Sushi Domains of Secreted GABAB1 Isoforms Selectively Impair GABAB Heteroreceptor Function J. Biol. Chem., November 7, 2008; 283(45): 31005 - 31011. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Callaghan, A. Haythornthwaite, G. Berecki, R. J. Clark, D. J. Craik, and D. J. Adams Analgesic {alpha}-Conotoxins Vc1.1 and Rg1A Inhibit N-Type Calcium Channels in Rat Sensory Neurons via GABAB Receptor Activation J. Neurosci., October 22, 2008; 28(43): 10943 - 10951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Vargas, M. Terunuma, J. A. Tello, M. N. Pangalos, S. J. Moss, and A. Couve The Availability of Surface GABAB Receptors Is Independent of {gamma}-Aminobutyric Acid but Controlled by Glutamate in Central Neurons J. Biol. Chem., September 5, 2008; 283(36): 24641 - 24648. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Mizuta, Y. Osawa, F. Mizuta, D. Xu, and C. W. Emala Functional Expression of GABAB Receptors in Airway Epithelium Am. J. Respir. Cell Mol. Biol., September 1, 2008; 39(3): 296 - 304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. W. Olsen and W. Sieghart International Union of Pharmacology. LXX. Subtypes of {gamma}-Aminobutyric AcidA Receptors: Classification on the Basis of Subunit Composition, Pharmacology, and Function. Update Pharmacol. Rev., September 1, 2008; 60(3): 243 - 260. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.-P. Li, Q. Yang, H.-M. Pan, and H.-L. Pan Plasticity of pre- and postsynaptic GABAB receptor function in the paraventricular nucleus in spontaneously hypertensive rats Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H807 - H815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Dittman and J. M. Kaplan Behavioral Impact of Neurotransmitter-Activated G-Protein-Coupled Receptors: Muscarinic and GABAB Receptors Regulate Caenorhabditis elegans Locomotion J. Neurosci., July 9, 2008; 28(28): 7104 - 7112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Mutolo, F. Bongianni, E. Cinelli, G. A. Fontana, and T. Pantaleo Modulation of the cough reflex by antitussive agents within the caudal aspect of the nucleus tractus solitarii in the rabbit Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2008; 295(1): R243 - R251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. W. Zemkova, I. Bjelobaba, M. Tomic, H. Zemkova, and S. S. Stojilkovic Molecular, pharmacological and functional properties of GABAA receptors in anterior pituitary cells J. Physiol., July 1, 2008; 586(13): 3097 - 3111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P Plaha, S Filipovic, and S S Gill Induction of parkinsonian resting tremor by stimulation of the caudal zona incerta nucleus: a clinical study J. Neurol. Neurosurg. Psychiatry, May 1, 2008; 79(5): 514 - 521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Nomura, Y. Suzuki, A. Kakizuka, and H. Jingami Direct Detection of the Interaction between Recombinant Soluble Extracellular Regions in the Heterodimeric Metabotropic {gamma}-Aminobutyric Acid Receptor J. Biol. Chem., February 22, 2008; 283(8): 4665 - 4673. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Karpuk and A. Hayar Activation of Postsynaptic GABAB Receptors Modulates the Bursting Pattern and Synaptic Activity of Olfactory Bulb Juxtaglomerular Neurons J Neurophysiol, January 1, 2008; 99(1): 308 - 319. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Bonaventura, P. N. Catalano, A. Chamson-Reig, E. Arany, D. Hill, B. Bettler, F. Saravia, C. Libertun, and V. A. Lux-Lantos GABAB receptors and glucose homeostasis: evaluation in GABAB receptor knockout mice Am J Physiol Endocrinol Metab, January 1, 2008; 294(1): E157 - E167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Ulrich, V. Besseyrias, and B. Bettler Functional Mapping of GABAB-Receptor Subtypes in the Thalamus J Neurophysiol, December 1, 2007; 98(6): 3791 - 3795. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Ben-Ari, J.-L. Gaiarsa, R. Tyzio, and R. Khazipov GABA: A Pioneer Transmitter That Excites Immature Neurons and Generates Primitive Oscillations Physiol Rev, October 1, 2007; 87(4): 1215 - 1284. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Cheng, C. Tu, L. Rodriguez, T.-H. Chen, M. M. Dvorak, M. Margeta, M. Gassmann, B. Bettler, D. Shoback, and W. Chang Type B {gamma}-Aminobutyric Acid Receptors Modulate the Function of the Extracellular Ca2+-Sensing Receptor and Cell Differentiation in Murine Growth Plate Chondrocytes Endocrinology, October 1, 2007; 148(10): 4984 - 4992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Chang, C. Tu, Z. Cheng, L. Rodriguez, T.-H. Chen, M. Gassmann, B. Bettler, M. Margeta, L. Y. Jan, and D. Shoback Complex Formation with the Type B {gamma}-Aminobutyric Acid Receptor Affects the Expression and Signal Transduction of the Extracellular Calcium-sensing Receptor: STUDIES WITH HEK-293 CELLS AND NEURONS J. Biol. Chem., August 24, 2007; 282(34): 25030 - 25040. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Grampp, K. Sauter, B. Markovic, and D. Benke {gamma}-Aminobutyric Acid Type B Receptors Are Constitutively Internalized via the Clathrin-dependent Pathway and Targeted to Lysosomes for Degradation J. Biol. Chem., August 17, 2007; 282(33): 24157 - 24165. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Christiansen, A.-K. Meinild, A. A. Jensen, and H. Brauner-Osborne Cloning and Characterization of a Functional Human {gamma}-Aminobutyric Acid (GABA) Transporter, Human GAT-2 J. Biol. Chem., July 6, 2007; 282(27): 19331 - 19341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Fowler, P. Aryal, K. F. Suen, and P. A. Slesinger Evidence for association of GABAB receptors with Kir3 channels and regulators of G protein signalling (RGS4) proteins J. Physiol., April 1, 2007; 580(1): 51 - 65. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. H. Jacobson, B. Bettler, K. Kaupmann, and J. F. Cryan GABAB(1) Receptor Subunit Isoforms Exert a Differential Influence on Baseline but Not GABAB Receptor Agonist-Induced Changes in Mice J. Pharmacol. Exp. Ther., December 1, 2006; 319(3): 1317 - 1326. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Dupuis, D. Relkovic, L. Lhuillier, J. Mosbacher, and K. Kaupmann 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., December 1, 2006; 70(6): 2027 - 2036. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Osawa, D. Xu, D. Sternberg, J. R. Sonett, J. D'Armiento, R. A. Panettieri, and C. W. Emala Functional expression of the GABAB receptor in human airway smooth muscle Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L923 - L931. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Krystal, J. Staley, G. Mason, I. L. Petrakis, J. Kaufman, R. A. Harris, J. Gelernter, and J. Lappalainen {gamma}-Aminobutyric Acid Type A Receptors and Alcoholism: Intoxication, Dependence, Vulnerability, and Treatment. Arch Gen Psychiatry, September 1, 2006; 63(9): 957 - 968. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. H. Jacobson, P. H. Kelly, B. Bettler, K. Kaupmann, and J. F. Cryan GABAB(1) Receptor Isoforms Differentially Mediate the Acquisition and Extinction of Aversive Taste Memories. J. Neurosci., August 23, 2006; 26(34): 8800 - 8803. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Xie, T. L. Crowder, A. Yamanaka, Stephen. R. Morairty, R. D. LeWinter, T. Sakurai, and T. S. Kilduff GABAB receptor-mediated modulation of hypocretin/orexin neurones in mouse hypothalamus J. Physiol., July 15, 2006; 574(2): 399 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Moldavan, R. P. Irwin, and C. N. Allen Presynaptic GABAB Receptors Regulate Retinohypothalamic Tract Synaptic Transmission by Inhibiting Voltage-Gated Ca2+ Channels J Neurophysiol, June 1, 2006; 95(6): 3727 - 3741. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Diaz-Rios and M. W. Miller Target-Specific Regulation of Synaptic Efficacy in the Feeding Central Pattern Generator of Aplysia: Potential Substrates for Behavioral Plasticity? Biol. Bull., June 1, 2006; 210(3): 215 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Chen, N. Menendez-Roche, and E. Sher Differential Modulation by the GABAB Receptor Allosteric Potentiator 2,6-Di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl)-phenol (CGP7930) of Synaptic Transmission in the Rat Hippocampal CA1 Area J. Pharmacol. Exp. Ther., June 1, 2006; 317(3): 1170 - 1177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Uezono, M. Kanaide, M. Kaibara, R. Barzilai, N. Dascal, K. Sumikawa, and K. Taniyama Coupling of GABAB receptor GABAB2 subunit to G proteins: evidence from Xenopus oocyte and baby hamster kidney cell expression system Am J Physiol Cell Physiol, January 1, 2006; 290(1): C200 - C207. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P Tosetti, N Ferrand, I. C.-L. Brun, and J. L Gaiarsa Epileptiform activity triggers long-term plasticity of GABAB receptor signalling in the developing rat hippocampus J. Physiol., November 1, 2005; 568(3): 951 - 966. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sauter, T. Grampp, J.-M. Fritschy, K. Kaupmann, B. Bettler, H. Mohler, and D. Benke Subtype-selective Interaction with the Transcription Factor CCAAT/Enhancer-binding Protein (C/EBP) Homologous Protein (CHOP) Regulates Cell Surface Expression of GABAB Receptors J. Biol. Chem., September 30, 2005; 280(39): 33566 - 33572. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kanbara, K. Okamoto, S. Nomura, T. Kaneko, R. Shigemoto, H. Azuma, Y. Katsuoka, and M. Watanabe Cellular Localization of GABA and GABAB Receptor Subunit Proteins During Spermiogenesis in Rat Testis J Androl, July 1, 2005; 26(4): 485 - 493. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gassmann, C. Haller, Y. Stoll, S. A. Aziz, B. Biermann, J. Mosbacher, K. Kaupmann, and B. Bettler The RXR-Type Endoplasmic Reticulum-Retention/Retrieval Signal of GABAB1 Requires Distant Spacing from the Membrane to Function Mol. Pharmacol., July 1, 2005; 68(1): 137 - 144. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. C. Snead and K. M. Gibson {gamma}-Hydroxybutyric Acid N. Engl. J. Med., June 30, 2005; 352(26): 2721 - 2732. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
