Neurobiología
Dr. Daniel J. Calvo
JEFE DE GRUPO
Investigador Principal CONICET
El GABA es uno de los principales neurotransmisores inhibidores del sistema nervioso. Sus acciones están mediadas por dos clases de receptores, los receptores ionotrópicos GABAA y los receptores metabotrópicos GABAB. Los receptores GABAA son blanco para las intervenciones terapéuticas y un sitio de acción para los fármacos ansiolíticos, anticonvulsivos y sedantes/hipnóticos típicos, como las benzodiazepinas, los barbitúricos y los neuroesteroides. Nuestro grupo estudia la modulación de la neurotransmisión GABAérgica por intermediarios metabólicos, agentes del estrés oxidativo y efectores alostéricos de interés fisiológico y farmacológico, empleando un abordaje multidisciplinario que conjuga técnicas de biología molecular, bioquímica y electrofisiología.
GABA is one of the major inhibitory neurotransmitters in the nervous system and its actions are mediated via two classes of receptors, ionotropic GABAA receptors and metabotropic GABAB receptors. The GABAA receptors are critical targets for therapeutic interventions, and a site of action for typical anxiolytic, anticonvulsant, and sedative/hypnotic drugs, such as benzodiazepines, barbiturates and neurosteroids. Our group studies the modulation of GABAergic neurotransmission by metabolic redox intermediaries, oxidative stress agents, and allosteric effectors of physiological and pharmacological interest, using a multidisciplinary approach that combines molecular biology, biochemistry and electrophysiology techniques.
Líneas de Investigación:
Reactive Oxygen Species in the Regulation of the GABA Mediated Inhibitory Neurotransmission. Beltrán González AN, López Pazos MI, Calvo DJ. Neuroscience. 2020 Jul 15;439:137-145. doi: 10.1016/j.neuroscience.2019.05.064.
Negative modulation of the GABAAρ1 receptor function by l-cysteine. Beltrán González AN, Vicentini F, Calvo DJ. J Neurochem. 2018 Jan;144(1):50-57. doi: 10.1111/jnc.14237.
Organization of Circadian Behavior Relies on Glycinergic Transmission. Frenkel L, Muraro NI, Beltrán González AN, Marcora MS, Bernabó G, Hermann-Luibl C, Romero JI, Helfrich-Förster C, Castaño EM, Marino-Busjle C, Calvo DJ, Ceriani MF. Cell Rep. 2017 Apr 4;19(1):72-85. doi: 10.1016/j.celrep.2017.03.034.
Dynamic Regulation of the GABAA Receptor Function by Redox Mechanisms. Calvo DJ, Beltrán González AN. Mol Pharmacol. 2016 Sep;90(3):326-33. doi: 10.1124/mol.116.105205. Epub 2016 Jul 20.
Enhancement of tonic and phasic GABAergic currents following nitric oxide synthase inhibition in hippocampal CA1 pyramidal neurons. Gasulla J, Calvo DJ. Neurosci Lett. 2015 Mar 17;590:29-34. doi: 10.1016/j.neulet.2015.01.058.
Benzodiazepine modulation of homomeric GABAAρ1 receptors: differential effects of diazepam and 4′-chlorodiazepam. Beltrán González AN, Pomata PE, Goutman JD, Gasulla J, Chebib M, Calvo DJ. Eur J Pharmacol. 2014 Nov 15;743:24-30. doi: 10.1016/j.ejphar.2014.09.017.
An intracellular redox sensor for reactive oxygen species at the M3-M4 linker of GABAAρ1 receptors. Beltrán González AN, Gasulla J, Calvo DJ. Br J Pharmacol. 2014 May;171(9):2291-9. doi: 10.1111/bph.12581.
Quercetin antagonism of GABAAρ1 receptors is prevented by ascorbic acid through a redox-independent mechanism. Calero CI, Beltrán González AN, Gasulla J, Alvarez S, Evelson P, Calvo DJ. Eur J Pharmacol. 2013 Aug 15;714(1-3):274-80. doi: 10.1016/j.ejphar.2013.07.044.
Positive modulation of the α9α10 nicotinic cholinergic receptor by ascorbic acid. Boffi JC, Wedemeyer C, Lipovsek M, Katz E, Calvo DJ, Elgoyhen AB. Br J Pharmacol. 2013 Feb;168(4):954-65. doi: 10.1111/j.1476-5381.2012.02221.x.
Nitric oxide potentiation of the homomeric ρ1 GABA(C) receptor function. Gasulla J, Beltrán González AN, Calvo DJ. Br J Pharmacol. 2012 Nov;167(6):1369-77. doi: 10.1111/j.1476-5381.2012.02087.x.
A celebration of Franco-Argentinean neuroscience. Calvo DJ, Golombek DA, Shulz DE. J Physiol Paris. 2012 Jan;106(1-2):1. doi: 10.1016/j.jphysparis.2012.04.001.
Allosteric modulation of retinal GABA receptors by ascorbic acid. Calero CI, Vickers E, Moraga Cid G, Aguayo LG, von Gersdorff H, Calvo DJ. J Neurosci. 2011 Jun 29;31(26):9672-82. doi: 10.1523/JNEUROSCI.5157-10.2011.
Redox modulation of homomeric rho1 GABA receptors. Calero CI, Calvo DJ. J Neurochem. 2008 Jun 1;105(6):2367-74. doi: 10.1111/j.1471-4159.2008.05319.x.
A new inorganic photolabile protecting group for highly efficient visible light GABA uncaging. Zayat L, Noval MG, Campi J, Calero CI, Calvo DJ, Etchenique R. Chembiochem. 2007 Nov 23;8(17):2035-8. doi: 10.1002/cbic.200700354.
Functional activation by central monoamines of human dopamine D(4) receptor polymorphic variants coupled to GIRK channels in Xenopus oocytes. Wedemeyer C, Goutman JD, Avale ME, Franchini LF, Rubinstein M, Calvo DJ. Eur J Pharmacol. 2007 May 21;562(3):165-73. doi: 10.1016/j.ejphar.2007.01.055. Epub 2007 Feb 8.
Analysis of macroscopic ionic currents mediated by GABArho1 receptors during lanthanide modulation predicts novel states controlling channel gating. Goutman JD, Escobar AL, Calvo DJ. Br J Pharmacol. 2005 Dec;146(7):1000-9. doi: 10.1038/sj.bjp.0706411.
Studies on the mechanisms of action of picrotoxin, quercetin and pregnanolone at the GABA rho 1 receptor. Goutman JD, Calvo DJ. Br J Pharmacol. 2004 Feb;141(4):717-27. doi: 10.1038/sj.bjp.0705657. Epub 2004 Jan 19.
Flavonoid modulation of ionic currents mediated by GABA(A) and GABA(C) receptors. Goutman JD, Waxemberg MD, Doñate-Oliver F, Pomata PE, Calvo DJ. Eur J Pharmacol. 2003 Feb 14;461(2-3):79-87. doi: 10.1016/s0014-2999(03)01309-8.
Integrantes del grupo
Andrea N. Beltrán González
Investigadora Asistente CONICET Profesora Adjunta Regular FFyB, UBA
Manuel I. López Pazos
Becario Doctoral CONICET
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