Ballestero, J.A.; Plazas, P.V.; Kracun, S.; Gómez-Casati, M.E.; Taranda, J.; Rothlin, C.V.; Katz, E.; Millar, N.S.; Elgoyhen, A.B. "Effects of quinine, quinidine, and chloroquine on α9α10 nicotinic cholinergic receptors" (2005) Molecular Pharmacology. 68(3):822-829
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In this study, we report the effects of the quinoline derivatives quinine, its optical isomer quinidine, and chloroquine on α9α10-containing nicotinic acetylcholine receptors (nAChRs). The compounds blocked acetylcholine (ACh)-evoked responses in α9α10-injected Xenopus laevis oocytes in a concentration-dependent manner, with a rank order of potency of chloroquine (IC50 = 0.39 μM) > quinine (IC50 = 0.97 μM) ∼ quinidine (IC50 = 1.37 μM). Moreover, chloroquine blocked ACh-evoked responses on rat cochlear inner hair cells with an IC50 value of 0.13 μM, which is within the same range as that observed for recombinant receptors. Block by chloroquine was purely competitive, whereas quinine inhibited ACh currents in a mixed competitive and noncompetitive manner. The competitive nature of the blockage produced by the three compounds was confirmed by equilibrium binding experiments using [3H] methyllycaconitine. Binding affinities (Ki values) were 2.3, 5.5, and 13.0 μM for chloroquine, quinine, and quinidine, respectively. Block by quinine was found to be only slightly voltage-dependent, thus precluding open-channel block as the main mechanism of interaction of quinine with α9α10 nAChRs. The present results add to the pharmacological characterization of α9α10-containing nicotinic receptors and indicate that the efferent olivocochlear system that innervates the cochlear hair cells is a target of these ototoxic antimalarial compounds. Copyright © 2005 The American Society for Pharmacology and Experimental Therapeutics.


Documento: Artículo
Título:Effects of quinine, quinidine, and chloroquine on α9α10 nicotinic cholinergic receptors
Autor:Ballestero, J.A.; Plazas, P.V.; Kracun, S.; Gómez-Casati, M.E.; Taranda, J.; Rothlin, C.V.; Katz, E.; Millar, N.S.; Elgoyhen, A.B.
Filiación:Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
Departamento de Fisiología, Biología Molecular y Celular, FCEyN, Universidad de Buenos Aires, Buenos Aires, Argentina
Department of Pharmacology, University College London, London, United Kingdom
Salk Institute for Biological Studies, San Diego, CA, United States
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, CONICET-UBA, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina
Palabras clave:acetylcholine; antimalarial agent; chloroquine; nicotinic receptor; quinidine; quinine sulfate; receptor subunit; animal cell; article; binding affinity; cholinergic receptor blocking; cochlea; concentration response; controlled study; drug competition; drug effect; drug potency; drug receptor binding; evoked response; hair cell; human; human cell; IC 50; mouse; nonhuman; oocyte; priority journal; Xenopus laevis; Animals; Antimalarials; Chloroquine; Hair Cells, Inner; Quinidine; Quinine; Radioligand Assay; Rats; Rats, Sprague-Dawley; Receptors, Nicotinic; Recombinant Proteins; Xenopus laevis
Página de inicio:822
Página de fin:829
Título revista:Molecular Pharmacology
Título revista abreviado:Mol. Pharmacol.
CAS:acetylcholine, 51-84-3, 60-31-1, 66-23-9; chloroquine, 132-73-0, 3545-67-3, 50-63-5, 54-05-7; quinidine, 56-54-2; quinine sulfate, 804-63-7; Antimalarials; Chloroquine, 54-05-7; Quinidine, 56-54-2; Quinine, 130-95-0; Receptors, Nicotinic; Recombinant Proteins


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---------- APA ----------
Ballestero, J.A., Plazas, P.V., Kracun, S., Gómez-Casati, M.E., Taranda, J., Rothlin, C.V., Katz, E.,..., Elgoyhen, A.B. (2005) . Effects of quinine, quinidine, and chloroquine on α9α10 nicotinic cholinergic receptors. Molecular Pharmacology, 68(3), 822-829.
---------- CHICAGO ----------
Ballestero, J.A., Plazas, P.V., Kracun, S., Gómez-Casati, M.E., Taranda, J., Rothlin, C.V., et al. "Effects of quinine, quinidine, and chloroquine on α9α10 nicotinic cholinergic receptors" . Molecular Pharmacology 68, no. 3 (2005) : 822-829.
---------- MLA ----------
Ballestero, J.A., Plazas, P.V., Kracun, S., Gómez-Casati, M.E., Taranda, J., Rothlin, C.V., et al. "Effects of quinine, quinidine, and chloroquine on α9α10 nicotinic cholinergic receptors" . Molecular Pharmacology, vol. 68, no. 3, 2005, pp. 822-829.
---------- VANCOUVER ----------
Ballestero, J.A., Plazas, P.V., Kracun, S., Gómez-Casati, M.E., Taranda, J., Rothlin, C.V., et al. Effects of quinine, quinidine, and chloroquine on α9α10 nicotinic cholinergic receptors. Mol. Pharmacol. 2005;68(3):822-829.