Effects of quinine, quinidine, and chloroquine on α9α10 nicotinic cholinergic receptors

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 concentrat...

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Autores principales:	Ballestero, Jimena A., Plazas, Paola Viviana, Gómez Casati, María Eugenia, Taranda, Julián, Katz, Eleonora
Publicado:	2005
Materias:	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
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0026895X_v68_n3_p822_Ballestero http://hdl.handle.net/20.500.12110/paper_0026895X_v68_n3_p822_Ballestero
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paper:paper_0026895X_v68_n3_p822_Ballestero2023-06-08T14:53:57Z Effects of quinine, quinidine, and chloroquine on α9α10 nicotinic cholinergic receptors Ballestero, Jimena A. Plazas, Paola Viviana Gómez Casati, María Eugenia Taranda, Julián Katz, Eleonora 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 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. Fil:Ballestero, J.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Plazas, P.V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Gómez-Casati, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Taranda, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Katz, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2005 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0026895X_v68_n3_p822_Ballestero http://hdl.handle.net/20.500.12110/paper_0026895X_v68_n3_p822_Ballestero
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 Ballestero, Jimena A. Plazas, Paola Viviana Gómez Casati, María Eugenia Taranda, Julián Katz, Eleonora Effects of quinine, quinidine, and chloroquine on α9α10 nicotinic cholinergic receptors
topic_facet	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
description	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.
author	Ballestero, Jimena A. Plazas, Paola Viviana Gómez Casati, María Eugenia Taranda, Julián Katz, Eleonora
author_facet	Ballestero, Jimena A. Plazas, Paola Viviana Gómez Casati, María Eugenia Taranda, Julián Katz, Eleonora
author_sort	Ballestero, Jimena A.
title	Effects of quinine, quinidine, and chloroquine on α9α10 nicotinic cholinergic receptors
title_short	Effects of quinine, quinidine, and chloroquine on α9α10 nicotinic cholinergic receptors
title_full	Effects of quinine, quinidine, and chloroquine on α9α10 nicotinic cholinergic receptors
title_fullStr	Effects of quinine, quinidine, and chloroquine on α9α10 nicotinic cholinergic receptors
title_full_unstemmed	Effects of quinine, quinidine, and chloroquine on α9α10 nicotinic cholinergic receptors
title_sort	effects of quinine, quinidine, and chloroquine on α9α10 nicotinic cholinergic receptors
publishDate	2005
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0026895X_v68_n3_p822_Ballestero http://hdl.handle.net/20.500.12110/paper_0026895X_v68_n3_p822_Ballestero
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_version_	1768546664351531008

Effects of quinine, quinidine, and chloroquine on α9α10 nicotinic cholinergic receptors

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