Substance P-induced skin inflammation is not modulated by a single dose of sitagliptin in human volunteers.

Détails

ID Serval
serval:BIB_DE9CEF3B5B9F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Substance P-induced skin inflammation is not modulated by a single dose of sitagliptin in human volunteers.
Périodique
Biological Chemistry
Auteur(s)
Grouzmann E., Bigliardi P., Appenzeller M., Pannatier A., Buclin T.
ISSN
1437-4315 (Electronic)
ISSN-L
1431-6730
Statut éditorial
Publié
Date de publication
2011
Volume
392
Numéro
3
Pages
217-221
Langue
anglais
Résumé
Substance P (SP), an undecapeptide belonging to the tachykinin family, is released during the activation of sensory nerves, and causes vasodilation, edema and pain through activation of tissular Neurokinin 1 receptors. SP proinflammatory effects are terminated by angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP), while the aminopeptidase dipeptidylpeptidase IV (DPPIV) can also play a role. The aim of this randomized, crossover, double-blind study was to assess the cutaneous vasoreactivity (flare and wheal reaction, burning pain sensation) to intradermal injection of ascending doses of SP in six volunteers receiving a single therapeutic dose of the DPPIV inhibitor sitagliptin or a matching placebo. Cutaneous SP challenges produced the expected, dose-dependent flare and wheal response, while eliciting mild to moderate local pain sensation with little dose dependency. However, no differences were shown in the responses observed under sitagliptin compared with placebo, while the study would have been sufficiently powered to detect a clinically relevant increase in sensitivity to SP. The results of this pilot study are in line with proteolytic cleavage of SP by ACE and NEP compensating the blockade of DPPIV to prevent an augmentation of its proinflammatory action.
Mots-clé
Capsaicin/administration & dosage, Carbonated Beverages, Cross-Over Studies, Dipeptidyl Peptidase 4/blood, Dipeptidyl Peptidase 4/drug effects, Dipeptidyl-Peptidase IV Inhibitors/administration & dosage, Dose-Response Relationship, Drug, Double-Blind Method, Drug Eruptions/drug therapy, Edema/chemically induced, Erythema/chemically induced, Humans, Injections, Intradermal, Male, Pain/chemically induced, Pyrazines/administration & dosage, Skin/drug effects, Substance P, Triazoles/administration & dosage, Vasodilation/drug effects
Pubmed
Web of science
Création de la notice
07/04/2011 10:01
Dernière modification de la notice
20/08/2019 17:03
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