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...
Guardado en:
| Autores principales: | , , , , , , , , |
|---|---|
| Formato: | JOUR |
| Materias: | |
| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_0026895X_v68_n3_p822_Ballestero |
| Aporte de: |
| id |
todo:paper_0026895X_v68_n3_p822_Ballestero |
|---|---|
| record_format |
dspace |
| spelling |
todo:paper_0026895X_v68_n3_p822_Ballestero2023-10-03T14:37:14Z Effects of quinine, quinidine, and chloroquine on α9α10 nicotinic cholinergic receptors 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. 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar 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, 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 |
| 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. |
| format |
JOUR |
| author |
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. |
| author_facet |
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. |
| author_sort |
Ballestero, J.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 |
| url |
http://hdl.handle.net/20.500.12110/paper_0026895X_v68_n3_p822_Ballestero |
| work_keys_str_mv |
AT ballesteroja effectsofquininequinidineandchloroquineona9a10nicotiniccholinergicreceptors AT plazaspv effectsofquininequinidineandchloroquineona9a10nicotiniccholinergicreceptors AT kracuns effectsofquininequinidineandchloroquineona9a10nicotiniccholinergicreceptors AT gomezcasatime effectsofquininequinidineandchloroquineona9a10nicotiniccholinergicreceptors AT tarandaj effectsofquininequinidineandchloroquineona9a10nicotiniccholinergicreceptors AT rothlincv effectsofquininequinidineandchloroquineona9a10nicotiniccholinergicreceptors AT katze effectsofquininequinidineandchloroquineona9a10nicotiniccholinergicreceptors AT millarns effectsofquininequinidineandchloroquineona9a10nicotiniccholinergicreceptors AT elgoyhenab effectsofquininequinidineandchloroquineona9a10nicotiniccholinergicreceptors |
| _version_ |
1782030375535509504 |