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Capsaicin-induced vasodilatation in human nasal vasculature is mediated by modulation of cyclooxygenase-2 activity and abrogated by sulprostone

Koen Van Crombruggen UGent, Luc Van Nassauw, LARA DERYCKE UGent, Jean-Piere Timmermans, Gabriële Holtappels UGent, David Hall and Claus Bachert UGent (2011) NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY. 383(6). p.613-626
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 EP(1) prostanoid receptor antagonist SC19220 (10 mu M) and almost abolished by the selective COX-2 inhibitor NS398 (1 mu M) and the EP(1/3) receptor agonist sulprostone (0.1-10 nM), but not affected by the TRPV1-antagonists capsazepine (5 mu M), the neurokinin NK(1) receptor antagonist GR20517A (1 mu M), and the calcitonin-gene-related peptide (CGRP) receptor antagonist CGRP8-37 (100 nM). Spontaneously released PGE(2) and PGD(2) levels were significantly reduced in the presence of capsaicin. In conclusion, capsaicin-at concentrations clinically applied or under investigation for diverse disease backgrounds-induces a vasodilatory response in human nasal mucosa via a mechanism involving TRPV1-independent reduction of PGE(2) production by modulation of COX-2 enzymatic activity. These vasodilatations can be suppressed by the EP(1/3) receptor agonist sulprostone at subnanomolar concentrations.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
Human nasal mucosa, Neurogenic inflammation, Vasodilatation, Capsaicin, COX-2, PGE(2), GENE-RELATED PEPTIDE, CAPSAZEPINE-INSENSITIVE RELAXATION, SEASONAL ALLERGIC RHINITIS, VANILLOID RECEPTOR TRPV1, TIME QUANTITATIVE PCR, PROSTAGLANDIN E-2, SUBSTANCE-P, PHARMACOLOGICAL CHARACTERIZATION, NEUROGENIC INFLAMMATION, MIGRAINE HEADACHE
journal title
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
Naunyn-Schmiedebergs Arch. Pharmacol.
volume
383
issue
6
pages
613 - 626
Web of Science type
Article
Web of Science id
000290547000007
JCR category
PHARMACOLOGY & PHARMACY
JCR impact factor
2.647 (2011)
JCR rank
101/259 (2011)
JCR quartile
2 (2011)
ISSN
0028-1298
DOI
10.1007/s00210-011-0638-6
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1255996
handle
http://hdl.handle.net/1854/LU-1255996
date created
2011-06-07 12:24:31
date last changed
2012-01-25 16:30:13
@article{1255996,
  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 EP(1) prostanoid receptor antagonist SC19220 (10 mu M) and almost abolished by the selective COX-2 inhibitor NS398 (1 mu M) and the EP(1/3) receptor agonist sulprostone (0.1-10 nM), but not affected by the TRPV1-antagonists capsazepine (5 mu M), the neurokinin NK(1) receptor antagonist GR20517A (1 mu M), and the calcitonin-gene-related peptide (CGRP) receptor antagonist CGRP8-37 (100 nM). Spontaneously released PGE(2) and PGD(2) levels were significantly reduced in the presence of capsaicin. 
In conclusion, capsaicin-at concentrations clinically applied or under investigation for diverse disease backgrounds-induces a vasodilatory response in human nasal mucosa via a mechanism involving TRPV1-independent reduction of PGE(2) production by modulation of COX-2 enzymatic activity. These vasodilatations can be suppressed by the EP(1/3) receptor agonist sulprostone at subnanomolar concentrations.},
  author       = {Van Crombruggen, Koen and Van Nassauw, Luc and DERYCKE, LARA and Timmermans, Jean-Piere and Holtappels, Gabri{\"e}le and Hall, David and Bachert, Claus},
  issn         = {0028-1298},
  journal      = {NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY},
  keyword      = {Human nasal mucosa,Neurogenic inflammation,Vasodilatation,Capsaicin,COX-2,PGE(2),GENE-RELATED PEPTIDE,CAPSAZEPINE-INSENSITIVE RELAXATION,SEASONAL ALLERGIC RHINITIS,VANILLOID RECEPTOR TRPV1,TIME QUANTITATIVE PCR,PROSTAGLANDIN E-2,SUBSTANCE-P,PHARMACOLOGICAL CHARACTERIZATION,NEUROGENIC INFLAMMATION,MIGRAINE HEADACHE},
  language     = {eng},
  number       = {6},
  pages        = {613--626},
  title        = {Capsaicin-induced vasodilatation in human nasal vasculature is mediated by modulation of cyclooxygenase-2 activity and abrogated by sulprostone},
  url          = {http://dx.doi.org/10.1007/s00210-011-0638-6},
  volume       = {383},
  year         = {2011},
}

Chicago
Van Crombruggen, Koen, Luc Van Nassauw, LARA DERYCKE, Jean-Piere Timmermans, Gabriële Holtappels, David Hall, and Claus Bachert. 2011. “Capsaicin-induced Vasodilatation in Human Nasal Vasculature Is Mediated by Modulation of Cyclooxygenase-2 Activity and Abrogated by Sulprostone.” Naunyn-schmiedebergs Archives of Pharmacology 383 (6): 613–626.
APA
Van Crombruggen, K., Van Nassauw, L., DERYCKE, L., Timmermans, J.-P., Holtappels, G., Hall, D., & Bachert, C. (2011). Capsaicin-induced vasodilatation in human nasal vasculature is mediated by modulation of cyclooxygenase-2 activity and abrogated by sulprostone. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 383(6), 613–626.
Vancouver
1.
Van Crombruggen K, Van Nassauw L, DERYCKE L, Timmermans J-P, Holtappels G, Hall D, et al. Capsaicin-induced vasodilatation in human nasal vasculature is mediated by modulation of cyclooxygenase-2 activity and abrogated by sulprostone. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY. 2011;383(6):613–26.
MLA
Van Crombruggen, Koen, Luc Van Nassauw, LARA DERYCKE, et al. “Capsaicin-induced Vasodilatation in Human Nasal Vasculature Is Mediated by Modulation of Cyclooxygenase-2 Activity and Abrogated by Sulprostone.” NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY 383.6 (2011): 613–626. Print.