{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:55:09Z","timestamp":1790362509215,"version":"4.1.0"},"reference-count":61,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2006,12,1]],"date-time":"2006-12-01T00:00:00Z","timestamp":1164931200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2006,12]]},"abstract":"<jats:p>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 \u03b17-nAChRs on cerebral perivascular sympathetic neurons mediate cerebral parasympathetic-nitrergic vasodilation, effects of physostigmine, neostigmine, and galantamine on \u03b17-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 ChEl inhibition of dilation induced by TNS but not by choline or nicotine was prevented by atropine (0.1 \u03bcmol\/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 \u03b17-nAChR-expressed Xenopus oocytes, nicotine-induced inward currents were attenuated by \u03b1-bungarotoxin and ChEIs. Moreover, ChEI inhibition of nicotine- and choline-induced dilation was prevented by pretreatment with mevastatin and lovastatin (10 \u03bcmol\/L), which did not affect ChEI inhibition of TNS-induced relaxation. These findings suggest that ChEIs inhibit the \u03b17-nAChRs located on postganglionic sympathetic nerve terminals of SCG origin, causing a decreased release of nitric oxide in the neighboring nitrergic nerves and cerebral vasodilation. Inhibition of \u03b17-nAChRs leading to a potential cerebral hypoperfusion may contribute to the limitation of ChEIs and question the validity of using a ChEI alone in treating AD. The efficacy of ChEIs may be improved by concurrent use of statins.<\/jats:p>","DOI":"10.1038\/sj.jcbfm.9600310","type":"journal-article","created":{"date-parts":[[2006,4,26]],"date-time":"2006-04-26T16:51:59Z","timestamp":1146070319000},"page":"1562-1576","source":"Crossref","is-referenced-by-count":26,"title":["Cholinesterase Inhibitor Blockade and its Prevention by Statins of Sympathetic \u03b17-nAChR-Mediated Cerebral Nitrergic Neurogenic Vasodilation"],"prefix":"10.1177","volume":"26","author":[{"given":"Mansoor","family":"Mozayan","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Fang","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Tzu Chi University Center for Vascular Medicine, College of Life Sciences, Neuro-Medical Scientific Center, Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minliang","family":"Si","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Tzu Chi University Center for Vascular Medicine, College of Life Sciences, Neuro-Medical Scientific Center, Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis S","family":"Premkumar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony JF","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois, USA"},{"name":"Institute of Pharmacology and Toxicology, Tzu Chi University Center for Vascular Medicine, College of Life Sciences, Neuro-Medical Scientific Center, Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2006,12,1]]},"reference":[{"key":"bibr1-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(98)00032-X"},{"key":"bibr2-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1126\/science.7046051"},{"key":"bibr3-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.118.1.23"},{"key":"bibr4-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200308844"},{"key":"bibr5-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1994.tb14793.x"},{"key":"bibr6-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1007\/BF02247419"},{"key":"bibr7-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16499-4"},{"key":"bibr8-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(90)90344-F"},{"key":"bibr9-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1124\/mol.64.5.1217"},{"key":"bibr10-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2003.09.004"},{"key":"bibr11-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1001\/jama.281.15.1401"},{"key":"bibr12-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.15.8880"},{"key":"bibr13-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-20-07993.2001"},{"key":"bibr14-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(97)00224-8"},{"key":"bibr15-sj.jcbfm.9600310","first-page":"339","volume":"181","author":"Fleming WW","year":"1972","journal-title":"J Pharmacol Exp Ther"},{"key":"bibr16-sj.jcbfm.9600310","unstructured":"Grady D (April 7, 2004) Minimal benefit is seen in drugs for Alzheimer's. New York Times."},{"key":"bibr17-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1099-1166(199703)12:3<295::AID-GPS476>3.0.CO;2-3"},{"key":"bibr18-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(92)90012-V"},{"key":"bibr19-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2005.04.012"},{"key":"bibr20-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.2174\/1381612043386509"},{"key":"bibr21-sj.jcbfm.9600310","first-page":"739","volume":"218","author":"Ignarro LJ","year":"1981","journal-title":"J Pharmacol Exp Ther"},{"key":"bibr22-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1987.00520150014011"},{"key":"bibr23-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)03155-X"},{"key":"bibr24-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10022"},{"key":"bibr25-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410420205"},{"key":"bibr26-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)00889-5"},{"key":"bibr27-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1007\/BF02255914"},{"key":"bibr28-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1982.50"},{"key":"bibr29-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.39.1.120"},{"key":"bibr30-sj.jcbfm.9600310","first-page":"H808","volume":"279","author":"Lee TJ-F","year":"2000","journal-title":"Am J Physiol"},{"key":"bibr31-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1097\/00008877-199911000-00014"},{"key":"bibr32-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2004.10.009"},{"key":"bibr33-sj.jcbfm.9600310","first-page":"H194","volume":"276","author":"Liu J","year":"1999","journal-title":"Am J Physiol"},{"key":"bibr34-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.302.1.397"},{"key":"bibr35-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200001000-00023"},{"key":"bibr36-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.2165\/00002512-200421070-00001"},{"key":"bibr37-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)00536-2"},{"key":"bibr38-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1990.4"},{"key":"bibr39-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1038\/npp.1994.11"},{"key":"bibr40-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1007\/BF01243353"},{"key":"bibr41-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.55.12.1182"},{"key":"bibr42-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119812"},{"key":"bibr43-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1016\/0306-9877(94)90153-8"},{"key":"bibr44-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.3109\/10799899309073670"},{"key":"bibr45-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-7061(97)00108-8"},{"key":"bibr46-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.59.2.223"},{"key":"bibr47-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(83)90017-3"},{"key":"bibr48-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.16.030193.002155"},{"key":"bibr49-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1126\/science.1720572"},{"key":"bibr50-sj.jcbfm.9600310","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/S0022-3565(24)29359-9","volume":"298","author":"Si ML","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"key":"bibr51-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000024417.79275.23"},{"key":"bibr52-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.046854"},{"key":"bibr53-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1254\/jjp.76.349"},{"key":"bibr54-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1007\/BF01271206"},{"key":"bibr55-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.302.6791.1491"},{"key":"bibr56-sj.jcbfm.9600310","unstructured":"Wei CY, Huang KC, Chou YH, Hsieh PF, Lin KH, Lin WW (2005) The role of Rho-associated kinase in differential regulat. Mol Pharmacol 2005, Nov 29; [E-pub ahead of print]."},{"key":"bibr57-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1999.00685.x"},{"key":"bibr58-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(95)00043-V"},{"key":"bibr59-sj.jcbfm.9600310","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)00548-4"},{"key":"bibr60-sj.jcbfm.9600310","first-page":"3","volume":"40","author":"Zdrenghea D","year":"2002","journal-title":"Rom J Intern Med"},{"key":"bibr61-sj.jcbfm.9600310","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/S0022-3565(24)37261-1","volume":"284","author":"Zhang W","year":"1998","journal-title":"J Pharmacol Exp Ther"}],"container-title":["Journal of Cerebral Blood Flow &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1038\/sj.jcbfm.9600310","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1038\/sj.jcbfm.9600310","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1038\/sj.jcbfm.9600310","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T14:01:36Z","timestamp":1741615296000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1038\/sj.jcbfm.9600310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,12]]},"references-count":61,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2006,12]]}},"alternative-id":["10.1038\/sj.jcbfm.9600310"],"URL":"https:\/\/doi.org\/10.1038\/sj.jcbfm.9600310","relation":{},"ISSN":["0271-678X","1559-7016"],"issn-type":[{"value":"0271-678X","type":"print"},{"value":"1559-7016","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,12]]}}}