Memantine Inhibits [alpha]3[beta]2-nAChRs-Mediated Nitrergic Neurogenic Vasodilation in Porcine Basilar Arteries

• Published in: PloS one 2012-07, Vol.7 (7), p.e40326
• Main Authors: Lee, Reggie Hui-Chao, Tseng, Ting-Yi, Wu, Celeste Yin-Chieh, Chen, Po-Yi, Chen, Mei-Fang, Kuo, Jon-Son, Lee, Tony Jer-Fu
• Format: Article
• Language: English
• Subjects: Advertising executives; Alzheimer's disease; Arteries; Nervous system agents; Neurons; Nitroprusside; Vasodilation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0040326

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 [alpha]3[beta]2-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 [alpha]3[beta]2-, [alpha]7- or [alpha]4[beta]2-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 [alpha]3[beta]2-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.