|
Title
|
|
|
|
Capsaicin-induced vasodilatation in human nasal vasculature is mediated by modulation of cyclooxygenase-2 activity and abrogated by sulprostone
| |
|
Author
|
|
|
|
| |
|
Abstract
|
|
|
|
| Extensively based on evidence gained from experimental animal models, the transient receptor potential vanilloid receptor type 1 (TRPV1)-activator capsaicin is regarded as a valuable tool in the research on neurogenic inflammation. Although capsaicin-related drugs gained renewed interest as a therapeutic tool, there is also controversy as whether neurogenic inflammation actually takes place in humans. In this study, we verified the involvement of capsaicin in vascular responses that are regarded to be implicated in the cascade of neurogenic inflammatory mechanisms. By means of ex vivo functional experiments on human nasal mucosal vascular beds, the effect and mechanism of action of capsaicin was assessed in the absence and presence of various agents that interfere with potentially related transduction pathways. Ten micromolars of capsaicin induced vasodilatations that were reduced by the selective EP1 prostanoid receptor antagonist SC19220 (10 μM) and almost abolished by the selective COX-2 inhibitor NS398 (1 μM) and the EP1/3 receptor agonist sulprostone (0.110 nM), but not affected by the TRPV1-antagonists capsazepine (5 μM), the neurokinin NK1 receptor antagonist GR20517A (1 μM), and the calcitonin-gene-related peptide (CGRP) receptor antagonist CGRP8-37 (100 nM). Spontaneously released PGE2 and PGD2 levels were significantly reduced in the presence of capsaicin. In conclusion, capsaicinat concentrations clinically applied or under investigation for diverse disease backgroundsinduces a vasodilatory response in human nasal mucosa via a mechanism involving TRPV1-independent reduction of PGE2 production by modulation of COX-2 enzymatic activity. These vasodilatations can be suppressed by the EP1/3 receptor agonist sulprostone at subnanomolar concentrations. |
| |
|
Language
|
|
|
|
English
| |
|
Source (journal)
|
|
|
|
Naunyn-Schmiedebergs archives of pharmacology. - Berlin
| |
|
Publication
|
|
|
|
Berlin
:
2011
| |
|
ISSN
|
|
|
|
0028-1298
[print]
1432-1912
[online]
| |
|
DOI
|
|
|
|
10.1007/S00210-011-0638-6
| |
|
Volume/pages
|
|
|
|
383
:6
(2011)
, p. 613-626
| |
|
ISI
|
|
|
|
000290547000007
| |
|
Full text (Publisher's DOI)
|
|
|
|
| |
|