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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22792283/pdf/?tool=EBI |
| _version_ | 1818722805605203968 |
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| author | Reggie Hui-Chao Lee Ting-Yi Tseng Celeste Yin-Chieh Wu Po-Yi Chen Mei-Fang Chen Jon-Son Kuo Tony Jer-Fu Lee |
| author_facet | Reggie Hui-Chao Lee Ting-Yi Tseng Celeste Yin-Chieh Wu Po-Yi Chen Mei-Fang Chen Jon-Son Kuo Tony Jer-Fu Lee |
| author_sort | Reggie Hui-Chao Lee |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-17T21:00:28Z |
| format | Article |
| id | doaj.art-6785d2e913f94094bc80a409e369fd61 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T21:00:28Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6785d2e913f94094bc80a409e369fd612022-12-21T21:32:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0177e4032610.1371/journal.pone.0040326Memantine inhibits α3β2-nAChRs-mediated nitrergic neurogenic vasodilation in porcine basilar arteries.Reggie Hui-Chao LeeTing-Yi TsengCeleste Yin-Chieh WuPo-Yi ChenMei-Fang ChenJon-Son KuoTony Jer-Fu LeeMemantine, 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22792283/pdf/?tool=EBI |
| spellingShingle | Reggie Hui-Chao Lee Ting-Yi Tseng Celeste Yin-Chieh Wu Po-Yi Chen Mei-Fang Chen Jon-Son Kuo Tony Jer-Fu Lee Memantine inhibits α3β2-nAChRs-mediated nitrergic neurogenic vasodilation in porcine basilar arteries. PLoS ONE |
| 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 |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22792283/pdf/?tool=EBI |
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