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Memantine Inhibits α3β2-nAChRs-Mediated Nitrergic Neurogenic Vasodilation in Porcine Basilar Arteries

Memantine, an NMDA receptor antagonist used for treatment of Alzheimer’s disease (AD), is known to block the nicotinic acetylcholine receptors (nAChRs) in the central nervous system (CNS). In the present study, we examined by wire myography if memantine inhibited α3β2-nAChRs located on cerebral peri...

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Autores principales: Lee, Reggie Hui-Chao, Tseng, Ting-Yi, Wu, Celeste Yin-Chieh, Chen, Po-Yi, Chen, Mei-Fang, Kuo, Jon-Son, Lee, Tony Jer-Fu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390354/
https://www.ncbi.nlm.nih.gov/pubmed/22792283
http://dx.doi.org/10.1371/journal.pone.0040326
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author Lee, Reggie Hui-Chao
Tseng, Ting-Yi
Wu, Celeste Yin-Chieh
Chen, Po-Yi
Chen, Mei-Fang
Kuo, Jon-Son
Lee, Tony Jer-Fu
author_facet Lee, Reggie Hui-Chao
Tseng, Ting-Yi
Wu, Celeste Yin-Chieh
Chen, Po-Yi
Chen, Mei-Fang
Kuo, Jon-Son
Lee, Tony Jer-Fu
author_sort Lee, Reggie Hui-Chao
collection PubMed
description Memantine, an NMDA receptor antagonist used for treatment of Alzheimer’s disease (AD), is known to block the nicotinic acetylcholine receptors (nAChRs) in the central nervous system (CNS). In the present study, we examined by wire myography if memantine inhibited α3β2-nAChRs located on cerebral perivascular sympathetic nerve terminals originating in the superior cervical ganglion (SCG), thus, leading to inhibition of nicotine-induced nitrergic neurogenic dilation of isolated porcine basilar arteries. Memantine concentration-dependently blocked nicotine-induced neurogenic dilation of endothelium-denuded basilar arteries without affecting that induced by transmural nerve stimulation, sodium nitroprusside, or isoproterenol. Furthermore, memantine significantly inhibited nicotine-elicited inward currents in Xenopous oocytes expressing α3β2-, α7- or α4β2-nAChR, and nicotine-induced calcium influx in cultured rat SCG neurons. These results suggest that memantine is a non-specific antagonist for nAChR. By directly inhibiting α3β2-nAChRs located on the sympathetic nerve terminals, memantine blocks nicotine-induced neurogenic vasodilation of the porcine basilar arteries. This effect of memantine is expected to reduce the blood supply to the brain stem and possibly other brain regions, thus, decreasing its clinical efficacy in the treatment of Alzheimer’s disease.
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spelling pubmed-33903542012-07-12 Memantine Inhibits α3β2-nAChRs-Mediated Nitrergic Neurogenic Vasodilation in Porcine Basilar Arteries Lee, Reggie Hui-Chao Tseng, Ting-Yi Wu, Celeste Yin-Chieh Chen, Po-Yi Chen, Mei-Fang Kuo, Jon-Son Lee, Tony Jer-Fu PLoS One Research Article Memantine, an NMDA receptor antagonist used for treatment of Alzheimer’s disease (AD), is known to block the nicotinic acetylcholine receptors (nAChRs) in the central nervous system (CNS). In the present study, we examined by wire myography if memantine inhibited α3β2-nAChRs located on cerebral perivascular sympathetic nerve terminals originating in the superior cervical ganglion (SCG), thus, leading to inhibition of nicotine-induced nitrergic neurogenic dilation of isolated porcine basilar arteries. Memantine concentration-dependently blocked nicotine-induced neurogenic dilation of endothelium-denuded basilar arteries without affecting that induced by transmural nerve stimulation, sodium nitroprusside, or isoproterenol. Furthermore, memantine significantly inhibited nicotine-elicited inward currents in Xenopous oocytes expressing α3β2-, α7- or α4β2-nAChR, and nicotine-induced calcium influx in cultured rat SCG neurons. These results suggest that memantine is a non-specific antagonist for nAChR. By directly inhibiting α3β2-nAChRs located on the sympathetic nerve terminals, memantine blocks nicotine-induced neurogenic vasodilation of the porcine basilar arteries. This effect of memantine is expected to reduce the blood supply to the brain stem and possibly other brain regions, thus, decreasing its clinical efficacy in the treatment of Alzheimer’s disease. Public Library of Science 2012-07-05 /pmc/articles/PMC3390354/ /pubmed/22792283 http://dx.doi.org/10.1371/journal.pone.0040326 Text en Lee et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lee, Reggie Hui-Chao
Tseng, Ting-Yi
Wu, Celeste Yin-Chieh
Chen, Po-Yi
Chen, Mei-Fang
Kuo, Jon-Son
Lee, Tony Jer-Fu
Memantine Inhibits α3β2-nAChRs-Mediated Nitrergic Neurogenic Vasodilation in Porcine Basilar Arteries
title Memantine Inhibits α3β2-nAChRs-Mediated Nitrergic Neurogenic Vasodilation in Porcine Basilar Arteries
title_full Memantine Inhibits α3β2-nAChRs-Mediated Nitrergic Neurogenic Vasodilation in Porcine Basilar Arteries
title_fullStr Memantine Inhibits α3β2-nAChRs-Mediated Nitrergic Neurogenic Vasodilation in Porcine Basilar Arteries
title_full_unstemmed Memantine Inhibits α3β2-nAChRs-Mediated Nitrergic Neurogenic Vasodilation in Porcine Basilar Arteries
title_short Memantine Inhibits α3β2-nAChRs-Mediated Nitrergic Neurogenic Vasodilation in Porcine Basilar Arteries
title_sort memantine inhibits α3β2-nachrs-mediated nitrergic neurogenic vasodilation in porcine basilar arteries
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390354/
https://www.ncbi.nlm.nih.gov/pubmed/22792283
http://dx.doi.org/10.1371/journal.pone.0040326
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