Block of the α9 nicotinic receptor by ototoxic aminoglycosides
In the present study, we report that the α9 nicotinic acetylcholine receptor (nAChR) expressed in Xenopus laevis oocytes is reversibly blocked by aminoglycoside antibiotics. The aminoglycosides tested blocked the α9 nAChR in a concentration-dependent manner with the following rank order of potency:...
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2000
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00283908_v39_n13_p2525_Rothlin http://hdl.handle.net/20.500.12110/paper_00283908_v39_n13_p2525_Rothlin |
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paper:paper_00283908_v39_n13_p2525_Rothlin2023-06-08T14:55:10Z Block of the α9 nicotinic receptor by ototoxic aminoglycosides Katz, Eleonora Verbitsky, Miguel Aminoglycosides Hair cells Nicotinic receptors Ototoxicity acetylcholine amikacin aminoglycoside aminoglycoside antibiotic agent gentamicin kanamycin neomycin nicotinic receptor streptomycin 1,2 bis(2 aminophenoxy)ethane N,N,N',N' tetraacetic acid acetoxymethyl ester 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester antiinfective agent calcium chelating agent Chrna9 protein, rat drug derivative egtazic acid gentamicin nicotinic receptor nicotinic receptor blocking agent animal cell article binding site controlled study Corti organ drug potency drug receptor binding hair cell nonhuman oocyte ototoxicity priority journal receptor blocking Xenopus laevis animal chemically induced disorder drug effect electrophysiology electrostimulation hearing disorder metabolism olivary nucleus rat Xenopus Animals Anti-Bacterial Agents Calcium Chelating Agents Egtazic Acid Electric Stimulation Electrophysiology Gentamicins Hearing Disorders Nicotinic Antagonists Olivary Nucleus Oocytes Rats Receptors, Nicotinic Xenopus In the present study, we report that the α9 nicotinic acetylcholine receptor (nAChR) expressed in Xenopus laevis oocytes is reversibly blocked by aminoglycoside antibiotics. The aminoglycosides tested blocked the α9 nAChR in a concentration-dependent manner with the following rank order of potency: neomycin>gentamicin>streptomycin>amikacin>kanamycin. The antagonistic effect of gentamicin was not overcome by increasing the concentration of acetylcholine (ACh), indicative of a non-competitive type of block. Blockage of ACh-evoked currents by gentamicin was found to be voltage-dependent, being more potent at hyperpolarized than at depolarized holding potentials. Furthermore, gentamicin blockage was dependent upon the extracellular Ca2+ concentration, shown by the fact that increments in extracellular Ca2+ significantly reduced the potency of this aminoglycoside to block the α9 nAChR. Possible mechanisms of blockage by the aminoglycosides are discussed. The present results suggest that the initial reversible actions of aminoglycosides at the organ of Corti, such as the elimination of the olivocochlear efferent function, are due in part to the interaction with the native α9-containing cholinergic receptor of the outer hair cells. Copyright (C) 2000 Elsevier Science Ltd. Fil:Katz, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Verbitsky, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2000 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00283908_v39_n13_p2525_Rothlin http://hdl.handle.net/20.500.12110/paper_00283908_v39_n13_p2525_Rothlin |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Aminoglycosides Hair cells Nicotinic receptors Ototoxicity acetylcholine amikacin aminoglycoside aminoglycoside antibiotic agent gentamicin kanamycin neomycin nicotinic receptor streptomycin 1,2 bis(2 aminophenoxy)ethane N,N,N',N' tetraacetic acid acetoxymethyl ester 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester antiinfective agent calcium chelating agent Chrna9 protein, rat drug derivative egtazic acid gentamicin nicotinic receptor nicotinic receptor blocking agent animal cell article binding site controlled study Corti organ drug potency drug receptor binding hair cell nonhuman oocyte ototoxicity priority journal receptor blocking Xenopus laevis animal chemically induced disorder drug effect electrophysiology electrostimulation hearing disorder metabolism olivary nucleus rat Xenopus Animals Anti-Bacterial Agents Calcium Chelating Agents Egtazic Acid Electric Stimulation Electrophysiology Gentamicins Hearing Disorders Nicotinic Antagonists Olivary Nucleus Oocytes Rats Receptors, Nicotinic Xenopus |
| spellingShingle |
Aminoglycosides Hair cells Nicotinic receptors Ototoxicity acetylcholine amikacin aminoglycoside aminoglycoside antibiotic agent gentamicin kanamycin neomycin nicotinic receptor streptomycin 1,2 bis(2 aminophenoxy)ethane N,N,N',N' tetraacetic acid acetoxymethyl ester 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester antiinfective agent calcium chelating agent Chrna9 protein, rat drug derivative egtazic acid gentamicin nicotinic receptor nicotinic receptor blocking agent animal cell article binding site controlled study Corti organ drug potency drug receptor binding hair cell nonhuman oocyte ototoxicity priority journal receptor blocking Xenopus laevis animal chemically induced disorder drug effect electrophysiology electrostimulation hearing disorder metabolism olivary nucleus rat Xenopus Animals Anti-Bacterial Agents Calcium Chelating Agents Egtazic Acid Electric Stimulation Electrophysiology Gentamicins Hearing Disorders Nicotinic Antagonists Olivary Nucleus Oocytes Rats Receptors, Nicotinic Xenopus Katz, Eleonora Verbitsky, Miguel Block of the α9 nicotinic receptor by ototoxic aminoglycosides |
| topic_facet |
Aminoglycosides Hair cells Nicotinic receptors Ototoxicity acetylcholine amikacin aminoglycoside aminoglycoside antibiotic agent gentamicin kanamycin neomycin nicotinic receptor streptomycin 1,2 bis(2 aminophenoxy)ethane N,N,N',N' tetraacetic acid acetoxymethyl ester 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester antiinfective agent calcium chelating agent Chrna9 protein, rat drug derivative egtazic acid gentamicin nicotinic receptor nicotinic receptor blocking agent animal cell article binding site controlled study Corti organ drug potency drug receptor binding hair cell nonhuman oocyte ototoxicity priority journal receptor blocking Xenopus laevis animal chemically induced disorder drug effect electrophysiology electrostimulation hearing disorder metabolism olivary nucleus rat Xenopus Animals Anti-Bacterial Agents Calcium Chelating Agents Egtazic Acid Electric Stimulation Electrophysiology Gentamicins Hearing Disorders Nicotinic Antagonists Olivary Nucleus Oocytes Rats Receptors, Nicotinic Xenopus |
| description |
In the present study, we report that the α9 nicotinic acetylcholine receptor (nAChR) expressed in Xenopus laevis oocytes is reversibly blocked by aminoglycoside antibiotics. The aminoglycosides tested blocked the α9 nAChR in a concentration-dependent manner with the following rank order of potency: neomycin>gentamicin>streptomycin>amikacin>kanamycin. The antagonistic effect of gentamicin was not overcome by increasing the concentration of acetylcholine (ACh), indicative of a non-competitive type of block. Blockage of ACh-evoked currents by gentamicin was found to be voltage-dependent, being more potent at hyperpolarized than at depolarized holding potentials. Furthermore, gentamicin blockage was dependent upon the extracellular Ca2+ concentration, shown by the fact that increments in extracellular Ca2+ significantly reduced the potency of this aminoglycoside to block the α9 nAChR. Possible mechanisms of blockage by the aminoglycosides are discussed. The present results suggest that the initial reversible actions of aminoglycosides at the organ of Corti, such as the elimination of the olivocochlear efferent function, are due in part to the interaction with the native α9-containing cholinergic receptor of the outer hair cells. Copyright (C) 2000 Elsevier Science Ltd. |
| author |
Katz, Eleonora Verbitsky, Miguel |
| author_facet |
Katz, Eleonora Verbitsky, Miguel |
| author_sort |
Katz, Eleonora |
| title |
Block of the α9 nicotinic receptor by ototoxic aminoglycosides |
| title_short |
Block of the α9 nicotinic receptor by ototoxic aminoglycosides |
| title_full |
Block of the α9 nicotinic receptor by ototoxic aminoglycosides |
| title_fullStr |
Block of the α9 nicotinic receptor by ototoxic aminoglycosides |
| title_full_unstemmed |
Block of the α9 nicotinic receptor by ototoxic aminoglycosides |
| title_sort |
block of the α9 nicotinic receptor by ototoxic aminoglycosides |
| publishDate |
2000 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00283908_v39_n13_p2525_Rothlin http://hdl.handle.net/20.500.12110/paper_00283908_v39_n13_p2525_Rothlin |
| work_keys_str_mv |
AT katzeleonora blockofthea9nicotinicreceptorbyototoxicaminoglycosides AT verbitskymiguel blockofthea9nicotinicreceptorbyototoxicaminoglycosides |
| _version_ |
1768541596744155136 |