GABAB receptors (GABABR) are metabotropic transmembrane receptors for gamma-aminobutyric acid (GABA) that are linked via G-proteins to potassium channels.[1] These receptors are found in the central and peripheral autonomic nervous system.[2] [edit] Functions They can stimulate the opening of K+ channels which brings the neuron closer to the equilibrium potential of K+, hyperpolarising the neuron. This prevents sodium channels from opening, action potentials from firing, and VDCCs from opening, and so stops neurotransmitter release. Thus GABAB receptors are considered inhibitory receptors. GABAB receptors can also reduce the activity of adenylyl cyclase and decrease the cell’s conductance to Ca2+.[2] GABAB receptors are involved in behavioral actions of ethanol, [3] gamma-Hydroxybutyric acid (GHB),[4] and possibly in pain.[5] Recent research suggests that these receptors may play an important developmental role. [6] [edit] Structure GABABRs are similar in structure to and in the same receptor family with metabotropic glutamate receptors.[7] There are two subtypes of the receptor, GABAB1 and GABAB2,[8][2] and these appear to assemble as heterodimers in neuronal membranes by linking up by their intracellular C termini.[2][7] It is speculated that binding of GABA causes the subunits to swing shut around the agonist like a venus fly trap.[2] [edit] Selective Ligands [edit] Agonists [edit] Positive Allosteric Modulators [edit] Antagonists - Saclofen
- Phaclofen
- phenylethylamine[13]
- SCH-50911
- CGP-52432: 3-([(3,4-Dichlorophenyl)methyl]amino]propyl) diethoxymethyl)phosphinic acid, CAS# 139667-74-6
- CGP-55845: (2S)-3-([(1S)-1-(3,4-Dichlorophenyl)ethyl]amino-2-hydroxypropyl)(phenylmethyl)phosphinic acid, CAS# 149184-22-5
- SGS-742 [14][15]
[edit] See also [edit] References - ^ Chen K, Li H, Ye N, Zhang J, Wang J (2005). "Role of GABAB receptors in GABA and baclofen-induced inhibition of adult rat cerebellar interpositus nucleus neurons in vitro". Brain Res Bull 67 (4): 310–8. doi:10.1016/j.brainresbull.2005.07.004. PMID 16182939.
- ^ a b c d e Martin I.L., and Dunn S.M.J. 2002. GABA receptors Tocris Cookson Ltd.
- ^ Dzitoyeva S, Dimitrijevic N, Manev H (2003). "Gamma-aminobutyric acid B receptor 1 mediates behavior-impairing actions of alcohol in Drosophila: adult RNA interference and pharmacological evidence". Proc Natl Acad Sci USA 100 (9): 5485–90. doi:10.1073/pnas.0830111100. PMID 12692303.
- ^ Dimitrijevic N, Dzitoyeva S, Satta R, Imbesi M, Yildiz S, Manev H (2005). "Drosophila GABA(B) receptors are involved in behavioral effects of gamma-hydroxybutyric acid (GHB)". Eur J Pharmacol 519 (3): 246–52. doi:10.1016/j.ejphar.2005.07.016. PMID 16129424.
- ^ Manev H, Dimitrijevic N (2004). "Drosophila model for in vivo pharmacological analgesia research". Eur J Pharmacol 491 (2-3): 207–8. doi:10.1016/j.ejphar.2004.03.030. PMID 15140638.
- ^ Dzitoyeva S, Gutnov A, Imbesi M, Dimitrijevic N, Manev H (2005). "Developmental role of GABAB(1) receptors in Drosophila". Brain Res Dev Brain Res 158 (1-2): 111–4. doi:10.1016/j.devbrainres.2005.06.005. PMID 16054235.
- ^ a b MRC (Medical Research Council). 2003. Glutamate receptors: Structures and functions. University of Brisotol Centre for Synaptic Plasticity.
- ^ Purves D., Augustine G.J., Fitzpatrick D., Katz L.C., LaMantia A.S., McNamara J.O., and Williams S.M. 2001. Neuroscience, Second Edition. Sinauer Associates, Inc.
- ^ Urwyler S, Mosbacher J, Lingenhoehl K, Heid J, Hofstetter K, Froestl W, Bettler B, Kaupmann K (November 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 (5): 963–71. PMID 11641424. http://molpharm.aspetjournals.org/cgi/content/abstract/60/5/963.
- ^ Adams CL, Lawrence AJ (2007). "CGP7930: a positive allosteric modulator of the GABAB receptor". CNS Drug Rev 13 (3): 308–16. doi:10.1111/j.1527-3458.2007.00021.x. PMID 17894647.
- ^ Paterson NE, Vlachou S, Guery S, Kaupmann K, Froestl W, Markou A (July 2008). "Positive modulation of GABA(B) receptors decreased nicotine self-administration and counteracted nicotine-induced enhancement of brain reward function in rats". J. Pharmacol. Exp. Ther. 326 (1): 306–14. doi:10.1124/jpet.108.139204. PMID 18445779.
- ^ Urwyler S, Pozza MF, Lingenhoehl K, Mosbacher J, Lampert C, Froestl W, Koller M, Kaupmann K (October 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 (1): 322–30. doi:10.1124/jpet.103.053074. PMID 12954816.
- ^ Berretta N, Giustizieri M, Bernardi G, Mercuri NB (November 2005). "Trace amines reduce GABA(B) receptor-mediated presynaptic inhibition at GABAergic synapses of the rat substantia nigra pars compacta". Brain Res. 1062 (1-2): 175–8. doi:10.1016/j.brainres.2005.09.009. PMID 16263097.
- ^ Froestl W, Gallagher M, Jenkins H, Madrid A, Melcher T, Teichman S, Mondadori CG, Pearlman R (October 2004). "SGS742: the first GABA(B) receptor antagonist in clinical trials". Biochemical Pharmacology 68 (8): 1479–87. doi:10.1016/j.bcp.2004.07.030. PMID 15451390.
- ^ Bullock R (January 2005). "SGS-742 Novartis". Current Opinion in Investigational Drugs (London, England : 2000) 6 (1): 108–13. PMID 15675610.
[edit] External links | Transmembrane receptor: G protein-coupled receptors | | | Class A: Rhodopsin like | | | | | | | | | | | | | | | GPR ( 1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 82, 83, 84, 85, 87, 88, 92, 101, 103, 109A, 109B, 119, 120, 132, 135, 137B, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 173, 174, 176, 177, 182) | | | | Adenosine ( A1, A2A, A2B, A3) · P2Y ( 1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14) | | | | | | | Other | Acetylcholine ( M1, M2, M3, M4, M5) · Adrenomedullin · Anaphylatoxin ( C3a, C5a) · Angiotensin ( 1, 2) · Apelin · Bile acid · Bombesin ( BRS3, GRPR, NMBR) · Bradykinin ( B1, B2) · Cannabinoid ( CB1, CB2) · Chemokine · Cholecystokinin ( A, B) · Dopamine ( D1, D2, D3, D4, D5) · EBI2 · Endothelin ( A, B) · Estrogen · Formyl peptide ( 1, 2, 3) · Free fatty acid ( 1, 2, 3, 4) · FSH · Galanin ( 1, 2, 3) · Gonadotropin-releasing hormone ( 1, 2) · GHB receptor · Ghrelin · Histamine ( H1, H2, H3, H4) · Kisspeptin · Luteinizing hormone/choriogonadotropin · lysophosphatidic acid ( 1, 2, 3) · Lysophospholipid ( 1, 2, 3, 4, 5, 6, 7, 8) · MAS ( 1, 1L, D, E, F, G, X1, X2, X3, X4) · Melanocortin ( 1, 2, 3, 4, 5) · MCHR ( 1, 2) · Melatonin ( 1A, 1B, 1C) · Niacin ( 1, 2) · Motilin · Opioid ( Delta, Kappa, Mu, Nociceptin & Zeta, but not Sigma) · Olfactory · Opsin ( 3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH) · Orexin ( 1, 2) · Oxytocin · Oxoglutarate · PAF · Prokineticin ( 1, 2) · Prolactin-releasing peptide · Protease-activated ( 1, 2, 3, 4) · Relaxin ( 1, 2, 3, 4) · Somatostatin ( 1, 2, 3, 4, 5) · Sphingosine-1-phosphate ( 1, 2, 3, 4, 5) · SREB · Succinate · TAAR ( 1, 2, 3, 5, 6, 8, 9) · Tachykinin ( 1, 2, 3) · Thyrotropin · Thyrotropin-releasing hormone · Urotensin-II · Vasopressin ( 1A, 1B, 2) | | | | Class B: Secretin like | | | GPR ( 56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 157) | | | Other | Brain-specific angiogenesis inhibitor ( 1, 2, 3) · Cadherin ( 1, 2, 3) · Calcitonin · CALCRL · CD97 · Corticotropin-releasing hormone ( 1, 2) · EMR ( 1, 2, 3) · Glucagon ( GR, GIPR, GLP1R, GLP2R) · Growth hormone releasing hormone · PACAPR1 · GPR · Latrophilin ( 1, 2, 3, ELTD1) · Methuselah-like proteins · Parathyroid hormone ( 1, 2) · Secretin · Vasoactive intestinal peptide ( 1, 2) | | | Class C: Metabotropic
glutamate / pheromone | | | TAS1R ( 1, 2, 3) · TAS2R ( 1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 38, 39, 40, 41, 43, 44, 45, 46, 47, 48, 49, 50) | | | Other | Calcium-sensing receptor · GABA B ( 1, 2) · Glutamate receptor ( Metabotropic glutamate ( 1, 2, 3, 4, 5, 6, 7, 8)) · GPRC6A · GPR ( 156, 158, 179) · RAIG ( 1, 2, 3, 4) | | | | Frizzled / Smoothened | | | |
