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Cholinergic neurotransmission links solitary chemosensory cells to nasal inflammation.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2014 Apr 22; Vol. 111 (16), pp. 6075-80. Date of Electronic Publication: 2014 Apr 07. - Publication Year :
- 2014
-
Abstract
- Solitary chemosensory cells (SCCs) of the nasal cavity are specialized epithelial chemosensors that respond to irritants through the canonical taste transduction cascade involving Gα-gustducin and transient receptor potential melastatin 5. When stimulated, SCCs trigger peptidergic nociceptive (or pain) nerve fibers, causing an alteration of the respiratory rate indicative of trigeminal activation. Direct chemical excitation of trigeminal pain fibers by capsaicin evokes neurogenic inflammation in the surrounding epithelium. In the current study, we test whether activation of nasal SCCs can trigger similar local inflammatory responses, specifically mast cell degranulation and plasma leakage. The prototypical bitter compound, denatonium, a well-established activator of SCCs, caused significant inflammatory responses in WT mice but not mice with a genetic deletion of elements of the canonical taste transduction cascade, showing that activation of taste signaling components is sufficient to trigger local inflammation. Chemical ablation of peptidergic trigeminal fibers prevented the SCC-induced nasal inflammation, indicating that SCCs evoke inflammation only by neural activity and not by release of local inflammatory mediators. Additionally, blocking nicotinic, but not muscarinic, acetylcholine receptors prevents SCC-mediated neurogenic inflammation for both denatonium and the bacterial signaling molecule 3-oxo-C12-homoserine lactone, showing the necessity for cholinergic transmission. Finally, we show that the neurokinin 1 receptor for substance P is required for SCC-mediated inflammation, suggesting that release of substance P from nerve fibers triggers the inflammatory events. Taken together, these results show that SCCs use cholinergic neurotransmission to trigger peptidergic trigeminal nociceptors, which link SCCs to the neurogenic inflammatory pathway.
- Subjects :
- Animals
Cell Degranulation
Chemoreceptor Cells metabolism
Extravasation of Diagnostic and Therapeutic Materials metabolism
Extravasation of Diagnostic and Therapeutic Materials pathology
Extravasation of Diagnostic and Therapeutic Materials physiopathology
Inflammation metabolism
Mast Cells physiology
Mice
Models, Biological
Nasal Mucosa metabolism
Nasal Mucosa pathology
Nasal Mucosa physiopathology
Nociceptors metabolism
Receptors, Neurokinin-1 metabolism
Receptors, Nicotinic metabolism
Signal Transduction
TRPM Cation Channels metabolism
Transducin metabolism
Trigeminal Nerve metabolism
Trigeminal Nerve pathology
Chemoreceptor Cells pathology
Cholinergic Neurons metabolism
Inflammation pathology
Inflammation physiopathology
Nose pathology
Nose physiopathology
Synaptic Transmission
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 111
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 24711432
- Full Text :
- https://doi.org/10.1073/pnas.1402251111