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 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.
Institute of Medical Sciences, College of Medicine, Tzu Chi University, Hualien, Taiwan.
Reggie Hui-Chao
RH
Lee
Ting-Yi
TY
Tseng
Celeste Yin-Chieh
CY
Wu
Po-Yi
PY
Chen
Mei-Fang
MF
Chen
Jon-Son
JS
Kuo
Tony Jer-Fu
TJ
Lee
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000502:physiology; D020013:Calcium Signaling; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008559:Memantine / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018408:Patch-Clamp Techniques; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism; D017783:Superior Cervical Ganglion / Q000187:drug effects / Q000378:metabolism; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*; D014982:Xenopus laevis; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579165:Chrna7 protein, rat; D018733:Nicotinic Antagonists; D020030:Nitric Oxide Donors; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C419362:nicotinic receptor alpha3beta2; C403531:nicotinic receptor alpha4beta2; D009599:Nitroprusside; D011189:Potassium Chloride; D009538:Nicotine; D007545:Isoproterenol; D008559:Memantine