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In many tissues, nicotine, acting through nicotinic acetylcholine receptors (nAChRs), has been shown to increase the release of the pro\u2010inflammatory mediator calcitonin gene\u2010related peptide (CGRP) thereby potentially contributing to neurogenic inflammation. The purpose of the present studies was to determine the effects of nicotine and other nAChR agonists on capsaicin\u2010evoked immunoreactive CGRP (iCGRP) release from rat buccal mucosa and to identify a potential cellular basis for these effects. Using a previously validated model of <jats:italic>in vitro<\/jats:italic> superfusion, we show that the nAChR agonists nicotine (EC<jats:sub>50<\/jats:sub> 557\u2003\u00b5<jats:sc>m<\/jats:sc>), epibatidine (EC<jats:sub>50<\/jats:sub> 317\u2003p<jats:sc>m<\/jats:sc>) and cytisine (EC<jats:sub>50<\/jats:sub> 4.83\u2003n<jats:sc>m<\/jats:sc>) potentiated capsaicin\u2010evoked iCGRP release in a concentration\u2010dependent manner by 123, 70 and 76%, respectively. The expression and distribution patterns of the mRNA transcripts encoding the \u03b13, \u03b14 and \u03b16 nAChR subunits and their colocalization with CGRP and the capsaicin receptor VR1 were examined in rat trigeminal ganglion using combined <jats:italic>in situ<\/jats:italic> hybridization and immunohistofluorescence. Of all trigeminal neurons counted, mRNA encoding the \u03b13, \u03b14 and \u03b16 subunits was found, respectively, in 14.45, 9.2 and 19.21% of neurons. The cell body diameter of most neurons containing any nAChR subunit was in the 30\u201340\u2003\u00b5m range with slightly fewer in the 20\u201330\u2003\u00b5m range. Co\u2010localization of these \u03b1 subunit transcripts with either CGRP or VR1 immunoreactivity ranged from approximately 5 to 7% for \u03b14 and over 8% for \u03b13 to 18% for \u03b16. These data support the hypothesis that nicotinic agents, acting at nAChRs contained on primary sensory neurons, are capable of directly modulating the stimulated release of iCGRP. In the case of users of nicotine\u2010containing tobacco products, this modulation could contribute to inflammatory processes within the oral cavity.<\/jats:p>","DOI":"10.1046\/j.1460-9568.2003.02935.x","type":"journal-article","created":{"date-parts":[[2003,11,13]],"date-time":"2003-11-13T23:54:19Z","timestamp":1068767659000},"page":"2515-2526","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Potentiation of evoked calcitonin gene\u2010related peptide release from oral mucosa: a potential basis for the pro\u2010inflammatory effects of nicotine"],"prefix":"10.1111","volume":"18","author":[{"given":"Gregory O.","family":"Dussor","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony S.","family":"Leong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas B.","family":"Gracia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonja","family":"Kilo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theodore J.","family":"Price","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth M.","family":"Hargreaves","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher M.","family":"Flores","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,11,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"crossref","first-page":"11 192","DOI":"10.1016\/S0021-9258(18)99147-7","article-title":"Neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes have a pentameric quaternary structure","volume":"266","author":"Anand R.","year":"1991","journal-title":"J. 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