title: Potentiation of evoked calcitonin gene-related peptide release from oral mucosa: a potential basis for the pro-inflammatory effects of nicotine.
abstract: Inflammation of the buccal mucosa, gingiva and periodontal tissues is a significant problem in users of nicotine-containing tobacco products; however, the potential role of nicotine in the development of this inflammation is unclear. In many tissues, nicotine, acting through nicotinic acetylcholine receptors (nAChRs), has been shown to increase the release of the pro-inflammatory mediator calcitonin gene-related 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-evoked immunoreactive CGRP (iCGRP) release from rat buccal mucosa and to identify a potential cellular basis for these effects. Using a previously validated model of in vitro superfusion, we show that the nAChR agonists nicotine (EC50 557 micro m), epibatidine (EC50 317 pm) and cytisine (EC50 4.83 nm) potentiated capsaicin-evoked iCGRP release in a concentration-dependent manner by 123, 70 and 76%, respectively. The expression and distribution patterns of the mRNA transcripts encoding the alpha3, alpha4 and alpha6 nAChR subunits and their colocalization with CGRP and the capsaicin receptor VR1 were examined in rat trigeminal ganglion using combined in situ hybridization and immunohistofluorescence. Of all trigeminal neurons counted, mRNA encoding the alpha3, alpha4 and alpha6 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 30-40 micro m range with slightly fewer in the 20-30 micro m range. Co-localization of these alpha subunit transcripts with either CGRP or VR1 immunoreactivity ranged from approximately 5 to 7% for alpha4 and over 8% for alpha3 to 18% for alpha6. 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-containing tobacco products, this modulation could contribute to inflammatory processes within the oral cavity.
authors: Department of Pharmacology, The University of Texas Health Science Center, San Antonio, TX, USA.
authors: Gregory O
authors: GO
authors: Dussor
authors: Anthony S
authors: AS
authors: Leong
authors: Nicholas B
authors: NB
authors: Gracia
authors: Sonja
authors: S
authors: Kilo
authors: Theodore J
authors: TJ
authors: Price
authors: Kenneth M
authors: KM
authors: Hargreaves
authors: Christopher M
authors: CM
authors: Flores
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001392:Azocines / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D017403:In Situ Hybridization; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009061:Mouth Mucosa / Q000378:metabolism*; D009538:Nicotine / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011807:Quinolizines / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000032:analysis / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000737:chemistry; D000093843:Quinolizidine Alkaloids
chemical_list: D000470:Alkaloids; D001392:Azocines; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D008464:Mecamylamine; D009538:Nicotine; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011725:Pyridines; D011807:Quinolizines; D011955:Receptors, Drug; D011978:Receptors, Nicotinic; C004712:cytisine; D000093843:Quinolizidine Alkaloids; C082748:epibatidine