Protease-activated receptor 2 expression in trigeminal neurons innervating the rat nasal mucosa.
Protease-activated receptor 2 (PAR2) is activated by trypsin and mast cell tryptase to induce widespread inflammation by unknown mechanisms. Trypsin and tryptase were shown to activate sensory neurons to release substance-P and related peptides to mediate neurogenic inflammation. In the present study, the expression of PAR2 and tachykinins were investigated in rat trigeminal neurons that were identified by retrograde labeling with rhodamine dye from the nasal mucosa by using neuronal tracing in combination with immunohistochemistry. We found that large subpopulation of all trigeminal neurons (43.5+/-2.6%) identified by the pan-neuronal marker PGP 9.5 were stained with PAR2-immunoreactivity. Of all trigeminal neurons, 7.5+/-2.1% were immunoreactive for tachykinins and PAR2, and only 3.9+/-1.7% of all trigeminal neurons expressed tachykinins, but not PAR2-immunoreactivity. The present study also found that a large number trigeminal neurons innervating the nasal mucosa expressed PAR2-immunoreactivity. Of the rhodamine-labeled trigeminal neurons, 52.5+/-1.8% were immunoreactive for only PAR2 expression, 7.3+/-1.9% contained tachykinins and PAR2, and 3.1+/-0.4 of the rhodamine-labeled trigeminal neurons were non-immunoreactive PAR2, but were positive for tachykinins-immunoreactivity. In conclusion, based on the co-localization of PAR2 and tachykinins in trigeminal sensory neurons innervating the nasal mucosa, the present study suggests that, following an activation of PAR2 receptor in tachykinergic neurons by trypsin and mast cell tryptase, there may be a triggering of tachykinin-mediated phenomena such as neurogenic inflammation in allergic or non-allergic rhinitis.
Dinh
Q Thai
QT
Department of Internal Medicine, Charité School of Medicine, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany. q-thai.dinh@charite.de
Cryer
Annette
A
Dinh
Stephen
S
Trevisani
Marcello
M
Georgiewa
Petra
P
Chung
Fan
F
Geppetti
Pierangelo
P
Heppt
Werner
W
Klapp
Burghard F
BF
Fischer
Axel
A
D000818:Animals; D015415:Biomarkers; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism; D008297:Male; D009297:Nasal Mucosa / Q000294:innervation*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D044464:Receptor, PAR-2 / Q000235:genetics / Q000378:metabolism*; D013194:Staining and Labeling / Q000379:methods; D015320:Tachykinins / Q000235:genetics / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000166:cytology*
D015415:Biomarkers; D044464:Receptor, PAR-2; D015320:Tachykinins