Cholinesterase inhibitor blockade and its prevention by statins of sympathetic alpha7-nAChR-mediated cerebral nitrergic neurogenic vasodilation

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Mansoor MozayanTony J F Lee

Abstract

Cholinesterase inhibitors (ChEIs) have been used to treat Alzheimer's disease (AD). The efficacy of these drugs, however, is less than satisfactory. The possibility that ChEIs may have effects unrelated to ChE activity, such as negatively modulate neuronal nicotinic acetylcholine receptors (nAChRs) was evaluated. Since alpha7-nAChRs on cerebral perivascular sympathetic neurons mediate cerebral parasympathetic-nitrergic vasodilation, effects of physostigmine, neostigmine, and galantamine on alpha7-nAChR-mediated dilation in isolated porcine basilar arterial rings denuded of endothelium was examined using in vitro tissue bath technique. The results indicated that these ChEIs blocked vasodilation induced by choline (0.3 mmol/L), nicotine (0.1 mmol/L), and transmural nerve stimulation (TNS). The ChEI inhibition of dilation induced by TNS but not by choline or nicotine was prevented by atropine (0.1 micromol/L) pretreatment. Furthermore, using confocal microscopy, significant calcium influx induced by choline and nicotine in cultured porcine superior cervical ganglion (SCG) cells was attenuated by ChEIs. In alpha7-nAChR-expressed Xenopus oocytes, nicotine-induced inward currents were attenuated by alpha-bungarotoxin and ChEIs. Moreo...Continue Reading

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Citations

Dec 6, 2008·Proceedings of the National Academy of Sciences of the United States of America·Hung Wen LinTony J-F Lee
Dec 17, 2010·Acta Physiologica·T J F LeeM F Chen
Feb 26, 2011·The International Journal of Neuroscience·Sangu MuthurajuGovindasamy Ilavazhagan
Jun 6, 2008·European Journal of Pharmacology·Mahmoud M El-MasAbdel-Rheem M Ghazal
Jul 21, 2009·Neuroscience Letters·Ken-ichi TanakaMasato Asanuma
Jun 5, 2016·Toxicology and Applied Pharmacology·Mei-Fang ChenTony Jer-Fu Lee
Jul 3, 2007·IEEE Transactions on Neural Systems and Rehabilitation Engineering : a Publication of the IEEE Engineering in Medicine and Biology Society·Donna Page, Marjan Jahanshahi
May 18, 2016·Experimental Biology and Medicine·Eugenia B ManukhinaRobert T Mallet
Jun 15, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Mansoor Mozayan, Tony J F Lee
May 4, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Reggie Hui-Chao LeeTony Jer-Fu Lee
Jan 3, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Hsi-Hsien ChangTony J F Lee

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Methods Mentioned

BETA
contocal microscopy

Software Mentioned

Fluoview
pClamp
Excel

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