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The present review updates current understanding of this action by substance P and compares it with other neuropeptides more recently found to modulate nAChRs in the autonomic nervous system.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Calcitonin gene\u2010related peptide (CGRP) and its N\u2010terminal fragments have been shown to exert complex inhibitory as well facilitatory actions on nAChRs. Fragments such as CGRP<jats:sub>1\u20134<\/jats:sub>, CGRP<jats:sub>1\u20135<\/jats:sub> and CGRP<jats:sub>1\u20136<\/jats:sub> rapidly and reversibly enhance agonist sensitivity of nAChRs without directly activating those receptors. Longer fragments or the full\u2010length peptide potently inhibit responses mediated by nAChRs <jats:italic>via<\/jats:italic> an apparently competitive\u2010type antagonism. This phenomenon differs from the substance P\u2010induced block, which is agonist use\u2010dependent and preferential towards large nicotinic responses.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>It is argued that the full\u2010length peptides CGRP and substance P might play distinct roles in the activity\u2010dependent modulation of cholinergic neurotransmission, by inhibiting background noise in the case of CGRP or by reducing excessive excitation in the case of substance P. Hence, multiple neuropeptide mechanisms may represent a wide array of fine\u2010tuning processes to regulate nicotinic synaptic transmission.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The availability of novel CGRP derivatives with a strong enhancing action on nAChRs may offer new leads for the drug design targeted for potentiation of nAChRs in the autonomic nervous system as well as in the brain, a subject of interest to counteract the deficit of the nAChR function associated with neurodegenerative diseases like Alzheimer's and Parkinson's diseases.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2003) <jats:bold>139<\/jats:bold>, 1061\u20131073. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705337\">10.1038\/sj.bjp.0705337<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705337","type":"journal-article","created":{"date-parts":[[2003,7,18]],"date-time":"2003-07-18T16:12:02Z","timestamp":1058544722000},"page":"1061-1073","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Modulation of neuronal nicotinic receptor function by the neuropeptides CGRP and substance P on autonomic nerve cells"],"prefix":"10.1111","volume":"139","author":[{"given":"Silvia","family":"Di Angelantonio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashid","family":"Giniatullin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Sokolova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Nistri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,30]]},"reference":[{"key":"e_1_2_20_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)91006-E"},{"key":"e_1_2_20_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(95)00308-6"},{"key":"e_1_2_20_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1983.tb11057.x"},{"key":"e_1_2_20_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/298240a0"},{"key":"e_1_2_20_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2001.281.6.C1871"},{"key":"e_1_2_20_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19980515)52:4<369::AID-JNR1>3.0.CO;2-7"},{"key":"e_1_2_20_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(99)00538-8"},{"key":"e_1_2_20_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(96)20050-5"},{"key":"e_1_2_20_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(96)10041-9"},{"key":"e_1_2_20_11_1","first-page":"253","article-title":"Calcitonin gene\u2010related peptide in the cardiovascular system: characterization of receptor populations and their (patho)physiological significance","volume":"48","author":"BELL D.","year":"1996","journal-title":"Pharmacol. 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