Potentiation of evoked calcitonin gene-related peptide release from oral mucosa: a potential basis for the pro-inflammatory effects of nicotine

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...

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Published in:The European journal of neuroscience Vol. 18; no. 9; pp. 2515 - 2526
Main Authors: Dussor, Gregory O., Leong, Anthony S., Gracia, Nicholas B., Kilo, Sonja, Price, Theodore J., Hargreaves, Kenneth M., Flores, Christopher M.
Format: Journal Article
Language:English
Published: Oxford, UK Blackwell Science, Ltd 01.11.2003
Subjects:
Alkaloids - pharmacology
Animals
Azocines - pharmacology
Bridged Bicyclo Compounds, Heterocyclic - pharmacology
buccal mucosa
Calcitonin Gene-Related Peptide - analysis
Calcitonin Gene-Related Peptide - metabolism
capsaicin
Capsaicin - pharmacology
cytisine
epibatidine
In Situ Hybridization
Male
Mecamylamine - pharmacology
Mouth Mucosa - metabolism
Nicotine - agonists
Nicotine - antagonists & inhibitors
Nicotine - pharmacology
nicotinic acetylcholine receptor
Nicotinic Agonists - pharmacology
Nicotinic Antagonists - pharmacology
Pyridines - pharmacology
Quinolizines - pharmacology
Radioimmunoassay
Rats
Rats, Sprague-Dawley
Receptors, Drug - analysis
Receptors, Drug - metabolism
Receptors, Nicotinic - analysis
Receptors, Nicotinic - drug effects
Receptors, Nicotinic - metabolism
sensory neuron
Trigeminal Ganglion - chemistry
ISSN:0953-816X, 1460-9568
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Summary: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 µm), 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 α3, α4 and α6 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 α3, α4 and α6 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 µm range with slightly fewer in the 20–30 µm range. Co‐localization of these α subunit transcripts with either CGRP or VR1 immunoreactivity ranged from approximately 5 to 7% for α4 and over 8% for α3 to 18% for α6. 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.
Bibliography:istex:2A29496DF29A528D3C73CB25FA5318040DEFA717
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ArticleID:EJN2935
On leave from Institut für Physiologie und Experimentelle Pathophysiologie, Universitätsstrasse 17, D‐91054 Erlangen, Germany.
Drug Discovery, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., Welsh and McKean Roads, Spring House, PA 19477‐0776, USA.
Present address
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Present address: Drug Discovery, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., Welsh and McKean Roads, Spring House, PA 19477-0776, USA.
On leave from Institut für Physiologie und Experimentelle Pathophysiologie, Universitätsstrasse 17, D-91054 Erlangen, Germany.
ISSN:0953-816X
1460-9568
DOI:10.1046/j.1460-9568.2003.02935.x