Artículo

Goutman, J.D.; Waxemberg, M.D.; Doñate-Oliver, F.; Pomata, P.E.; Calvo, D.J. "Flavonoid modulation of ionic currents mediated by GABAA and GABAC receptors" (2003) European Journal of Pharmacology. 461(2-3):79-87
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Abstract:

The modulation of ionotropic γ-aminobutyric acid (GABA) receptors (GABA-gated Cl- channels) by a group of natural and synthetic flavonoids was studied in electrophysiological experiments. Quercetin, apigenin, morine, chrysin and flavone inhibited ionic currents mediated by α1β1γ2s GABAA and ρ1 GABAC receptors expressed in Xenopus laevis oocytes in the micromolar range. α1β1γ2s GABAA and ρ1 GABAC receptors differ largely in their sensitivity to benzodiazepines, but they were similarly modulated by different flavonoids. Quercetin produced comparable actions on currents mediated by α4β2 neuronal nicotinic acetylcholine, serotonin 5-HT3A and glutamate AMPA/kainate receptors. Sedative and anxiolytic flavonoids, like chrysin or apigenin, failed to potentiate but antagonized α1β1γ2s GABAA receptors. Effects of apigenin and quercetin on α1β1γ2s GABAA receptors were insensitive to the benzodiazepine antagonist flumazenil. Results indicate that mechanism/s underlying the modulation of ionotropic GABA receptors by some flavonoids differs from that described for classic benzodiazepine modulation. © 2003 Elsevier Science B.V. All rights reserved.

Registro:

Documento: Artículo
Título:Flavonoid modulation of ionic currents mediated by GABAA and GABAC receptors
Autor:Goutman, J.D.; Waxemberg, M.D.; Doñate-Oliver, F.; Pomata, P.E.; Calvo, D.J.
Filiación:Inst. Invest. Ing. Genet. Biol. M., Vuelta de Obligado 2490, Capital Federal (1428), Buenos Aires, Argentina
Depto. Fisiol., Biol. Molec. y Cel., Fac. de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Departamento de Neurociencias, Fac. de Med. y Odontología, Universidad del País Vasco, Leioa, Spain
Palabras clave:Benzodiazepine; Flavonoid; GABA (γ-aminobutyric acid); GABAA receptor; GABAC receptor; 4 aminobutyric acid A receptor; 4 aminobutyric acid C receptor; acetylcholine; alpha naphthoflavone; AMPA receptor; anxiolytic agent; apigenin; benzodiazepine; brain receptor; chloride channel; chrysin; flavone; flavonoid; flumazenil; glutamate receptor; ionotropic receptor; kainic acid; kainic acid receptor; morin; nicotinic receptor; quercetin; receptor subunit; sedative agent; serotonin; serotonin 3 receptor; article; drug antagonism; drug effect; drug mechanism; electrophysiology; ion current; priority journal; protein expression; receptor sensitivity; Xenopus laevis
Año:2003
Volumen:461
Número:2-3
Página de inicio:79
Página de fin:87
DOI: http://dx.doi.org/10.1016/S0014-2999(03)01309-8
Título revista:European Journal of Pharmacology
Título revista abreviado:Eur. J. Pharmacol.
ISSN:00142999
CODEN:EJPHA
CAS:acetylcholine, 51-84-3, 60-31-1, 66-23-9; alpha naphthoflavone, 604-59-1; apigenin, 520-36-5; benzodiazepine, 12794-10-4; chrysin, 12624-02-1, 480-40-0; flavone, 525-82-6; flumazenil, 78755-81-4; kainic acid, 487-79-6; morin, 480-16-0; quercetin, 117-39-5; serotonin, 50-67-9
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00142999_v461_n2-3_p79_Goutman

Referencias:

  • Avallone, R., Zanoli, P., Puia, G., Kleinschnitz, M., Schreier, P., Baraldi, M., Pharmacological profile of apigenin, a flavonoid isolated from Matricaria chamomilla (2000) Biochem. Pharmacol., 59, pp. 1387-1394
  • Barnard, E.A., Skolnick, P., Olsen, R.W., Möhler, H., Sieghart, W., Biggio, G., Braestrup, C., Langer, S.Z., International Union of Pharmacology. XV. Subtypes of gamma-aminobutyric acidA receptors: Classification on the basis of subunit structure and receptor function (1998) Pharmacol. Rev., 50, pp. 291-313
  • Blaschke, M., Gremmels, D., Everts, I., Weigand, E., Heinemann, S.F., Hollmann, M., Keller, B.U., Pharmacological differentiation between neuronal and recombinant glutamate receptor channels expressed in Xenopus oocytes (1997) Neuropharmacology, 36, pp. 1489-1501
  • Bohm, B.A., Introduction to flavonoids (1998) Chemistry and Biochemistry of Organic Natural Products, , Amsterdam: Harwood Academic Publishers
  • Buisson, B., Gopalakrishnan, M., Arneric, S.P., Sullivan, J.P., Bertrand, D., Human α4β2 neuronal nicotinic acetylcholine receptor in HEK 293 cells: A patch-clamp study (1996) J. Neurosci., 16, pp. 7880-7891
  • Calvo, D.J., Goutman, J.D., Waxemberg, M.D., Doñate-Oliver, F., Pomata, P.E., Novel pharmacological effects of flavonoids: functional studies on ionotropic neurotransmitter receptors. Synaptic Transmission 100 years after L. Luciani (2000) Symposium in Honour of Ricardo Miledi, p. 25. , Rome, Italy. Org: F. Eusebi, F. Grassi, L. Negri, F. Ruzzier. Università di Roma "La Sapienza". Dipartimento di Fisiologia Umana e Farmacologia "V. Erspamer". Casa Editrice Scientifica Internazionale. Abstract
  • Chakravarthy, B.K., Rao, Y.V., Gambhir, S.S., Gode, K.D., Isolation of amentoflavone from Selaginella rupestris and its pharmacological activity on central nervous system, smooth muscles and isolated frog heart preparations (1981) Planta Med., 43, pp. 64-70
  • Cohen, Z., Bonvento, G., Lacombe, P., Hamel, E., Serotonin in the regulation of brain microcirculation (1996) Prog. Neurobiol., 50, pp. 335-362
  • Dekermendjian, K., Kahnberg, P., Witt, M.R., Sterner, O., Nielsen, M., Liljefors, T., Structure-activity relationships and molecular modeling analysis of flavonoids binding to the benzodiazepine site of the rat brain GABA(A) receptor complex (1999) J. Med. Chem., 42, pp. 4343-4350
  • Enz, R., Cutting, G.R., Molecular composition of GABAC receptors (1998) Vis. Res., 38, pp. 1431-1441
  • Frerking, M., Nicoll, R.A., Synaptic kainate receptors (2000) Curr. Opin. Neurobiol., 10, pp. 342-351
  • Griebel, G., Perrault, G., Tan, S., Schoemaker, H., Sanger, D.J., Pharmacological studies on synthetic flavonoids: Comparison with diazepam (1999) Neuropharmacology, 38, pp. 965-977
  • Gundersen, C.B., Miledi, R., Parker, I., Glutamate and kainate receptors induced by rat brain messenger RNA in Xenopus oocytes (1984) Proc. R. Soc. Lond., B Biol. Sci., 221, pp. 127-143
  • Häberlein, H., Tschiersch, K.P., Sächfer, H.L., Flavonoids from Leptospermum scoparium with affinity to the benzodiazepine receptor characterized by structure activity relationships and in vivo studies of a plant extract (1994) Pharmazie, 49, pp. 912-922
  • Harborne, J.B., Williams, C.A., Advances in flavonoid research since 1992 (2000) Phytochemistry, 55, pp. 481-504
  • Hevers, W., Luddens, H., The diversity of GABAA receptors. Pharmacological and electrophysiological properties of GABAA channel subtypes (1998) Mol. Neurobiol., 18, pp. 35-86
  • Ji, X.-D., Melman, N., Jacobson, K.A., Interactions of flavonoids and other phytochemicals with adenosine receptors (1996) J. Med. Chem., 39, pp. 781-788
  • Koh, D.S., Reid, G., Vogel, W., Activating effect of the flavonoid phloretin on Ca2+-activated K+ channels in myelinated nerve fibers of Xenopus laevis (1994) Neurosci. Lett., 165, pp. 167-170
  • Mall, M., Wissner, A., Seydewitz, H.H., Hubner, M., Kuehr, J., Brandis, M., Greger, R., Kunzelmann, K., Effect of genistein on native epithelial tissue from normal individuals and CF patients and on ion channels expressed in Xenopus oocytes (2000) Br. J. Pharmacol., 130, pp. 1884-1892
  • Marder, M., Viola, H., Wasowski, C., Wolfman, C., Waterman, P.G., Medina, J.H., Paladini, A.C., 6,3′-Dinitroflavone, a novel high affinity ligand for the benzodiazepine receptor with potent anxiolytic properties (1995) Bioorg. Med. Chem. Lett., 5, pp. 2717-2720
  • Marder, M., Paladini, A.C., GABAA-receptor ligands of flavonoid structure (2002) Curr. Top. Med. Chem., 2, pp. 853-867
  • Medina, J.H., Paladini, A.C., Wolfman, C., Levi de Stein, M., Calvo, D.J., Díaz, L.E., Peña, C., Chrysin (5,7-di-OH flavone), a naturally-occurring ligand for benzodiazepine receptors, with anticonvulsant properties (1990) Biochem. Pharmacol., 40, pp. 2227-2232
  • Medina, J.H., Viola, H., Wolfman, C., Marder, M., Wasowski, C., Calvo, D.J., Paladini, A.C., Neuroactive flavonoids: New ligands for the benzodiazepine receptors (1998) Phytomedicine, 5, pp. 235-243
  • Middleton, E., Kandaswami, C., The impact of plant flavonoids on mammalian biology: Implications for immunity, inflammation and cancer (1994) The Flavonoids, pp. 619-645. , J.B. Harbone. London: Chapman & Hall
  • Miksicek, R.J., Commonly occurring plant flavonoids have estrogenic activity (1993) Mol. Pharmacol., 44, pp. 37-43
  • Miledi, R., Parker, I., Cl- current induced by injection of calcium into Xenopus oocytes (1984) J. Physiol., 357, pp. 173-183
  • Miledi, R., Parker, I., Sumikawa, K., Transplanting receptors from brain into oocytes (1989) Fidia Research Foundation Neuroscience Award Lecture, pp. 57-89. , J. Smith. New York, NY: Raven Press
  • Movileanu, L., Neagoe, I., Flonta, M.L., Interaction of the antioxidant flavonoid quercetin with planar lipid bilayers (2000) Int. J. Pharm., 205, pp. 135-146
  • Nielsen, M., Frøkjaer, S., Braestrup, C., High affinity of the naturally-occurring biflavonoid, amentoflavone, to brain benzodiazepine receptors in vitro (1988) Biochem. Pharmacol., 37, pp. 3285-3287
  • Oyama, Y., Fuchs, P.A., Katayama, N., Noa, K., Myricetin and quercetin, the flavonoid constituents of Ginkgo biloba extract, greatly reduce oxidative metabolism in both resting and Ca2+-loaded brain neurons (1994) Brain Res., 635, pp. 125-129
  • Pattichis, K., Louca, L.L., Jarman, J., Sandler, M., Glover, V., 5-Hydroxytryptamine release from platelets by different red wines: Implications for migraine (1995) Eur. J. Pharmacol., 13, pp. 173-177
  • Picq, M., Cheav, S.V., Prigent, A.F., Effect of two flavonoid compounds on the central nervous system. Analgesic activity (1991) Life Sci., 49, pp. 1979-1988
  • Ramassamy, C., Christen, Y., Clostre, F., Costentin, J., The Ginkgo biloba extract, EGb761, increases synaptosomal uptake of 5-hydroxytryptamine: In-vitro and ex-vivo studies (1992) J. Pharm. Pharmacol., 44, pp. 943-945
  • Salgueiro, J.B., Ardenghi, P., Dias, M., Ferreira, M.B., Izquierdo, I., Medina, J.H., Anxiolytic natural and synthetic flavonoid ligands of the central benzodiazepine receptor have no effect on memory tasks in rats (1997) Pharmacol. Biochem. Behav., 58, pp. 887-891
  • Saponara, S., Sgaragli, G., Fusi, F., Quercetin as a novel activator of L-type Ca(2+) channels in rat tail artery smooth muscle cells (2002) Br. J. Pharmacol., 135, pp. 1819-1827
  • Simmen, U., Schweitzer, C., Burkard, W., Schaffner, W., Lundstrom, K., Hypericum perforatum inhibits the binding of mu- and kappa-opioid receptor expressed with the Semliki Forest virus system (1998) Pharm. Acta Helv., 73, pp. 53-56
  • Speroni, E., Minghetti, A., Neuropharmacological activity of extracts from Passiflora incarnata (1988) Planta Med., 54, pp. 488-491
  • Van Hooft, J.A., Vijverberg, H.P., 5-HT3 receptors and neurotransmitter release in the CNS: A nerve ending story? (2000) Trends Neurosci., 23, pp. 605-610
  • Viola, H., Wasowski, C., Levi de Stein, M., Wolfman, C., Silveira, R., Dajas, F., Medina, J.H., Paladini, A.C., Apigenin, a component of Matricaria recutita flowers is a central benzodiazepine receptors-ligand with anxiolytic effects (1995) Planta Med., 61, pp. 11-14
  • Viola, H., Wolfman, C., Marder, M., Goutman, J.D., Wasowski, C., Calvo, D.J., Izquierdo, I., Medina, J.H., 6-Chlorine-3′-nitroflavone is a potent central benzodiazepine receptor ligand devoid of intrinsic activity (2000) Pharmacol. Biochem. Behav., 65, pp. 313-320
  • Vohora, S.B., Kumar, I., Shah, S.A., Khan, M.S.Y., Effect of biflavonoids of Taxus baccata on the central nervous system (1980) Indian J. Med. Res., 71, pp. 815-820
  • Wolfman, C., Viola, H., Paladini, A.C., Dajas, F., Medina, J.H., Possible anxiolytic effects of chrysin, a central benzodiazepine receptor ligand isolated from Passiflora coerulea (1994) Pharmacol. Biochem. Behav., 47, pp. 1-4
  • Zhang, D., Pan, Z.H., Awobuluyi, M., Lipton, S.A., Structure and function of GABA(C) receptors: A comparison of native versus recombinant receptors (2001) Trends Pharmacol. Sci., 22 (3), pp. 121-132

Citas:

---------- APA ----------
Goutman, J.D., Waxemberg, M.D., Doñate-Oliver, F., Pomata, P.E. & Calvo, D.J. (2003) . Flavonoid modulation of ionic currents mediated by GABAA and GABAC receptors. European Journal of Pharmacology, 461(2-3), 79-87.
http://dx.doi.org/10.1016/S0014-2999(03)01309-8
---------- CHICAGO ----------
Goutman, J.D., Waxemberg, M.D., Doñate-Oliver, F., Pomata, P.E., Calvo, D.J. "Flavonoid modulation of ionic currents mediated by GABAA and GABAC receptors" . European Journal of Pharmacology 461, no. 2-3 (2003) : 79-87.
http://dx.doi.org/10.1016/S0014-2999(03)01309-8
---------- MLA ----------
Goutman, J.D., Waxemberg, M.D., Doñate-Oliver, F., Pomata, P.E., Calvo, D.J. "Flavonoid modulation of ionic currents mediated by GABAA and GABAC receptors" . European Journal of Pharmacology, vol. 461, no. 2-3, 2003, pp. 79-87.
http://dx.doi.org/10.1016/S0014-2999(03)01309-8
---------- VANCOUVER ----------
Goutman, J.D., Waxemberg, M.D., Doñate-Oliver, F., Pomata, P.E., Calvo, D.J. Flavonoid modulation of ionic currents mediated by GABAA and GABAC receptors. Eur. J. Pharmacol. 2003;461(2-3):79-87.
http://dx.doi.org/10.1016/S0014-2999(03)01309-8