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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


IMPACT FACTOR 2018: 3.014
5-year IMPACT FACTOR: 3.162

CiteScore 2018: 3.09

SCImago Journal Rank (SJR) 2018: 1.482
Source Normalized Impact per Paper (SNIP) 2018: 0.820

Online
ISSN
1437-4315
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Volume 392, Issue 3

Issues

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

Eric Grouzmann / Paul Bigliardi / Monique Appenzeller
  • Division de Pharmacologie et Toxicologie Cliniques, CHU Vaudois, CH-1011 Lausanne, Switzerland
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ André Pannatier / Thierry Buclin
  • Division de Pharmacologie et Toxicologie Cliniques, CHU Vaudois, CH-1011 Lausanne, Switzerland
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2011-06-18 | DOI: https://doi.org/10.1515/bc.2011.003

Abstract

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.

Keywords: clinical trial; dipeptidylpeptidase IV; flare; proteases; tachykinin; wheal

About the article

Corresponding author


Received: 2010-07-12

Accepted: 2010-08-23

Published Online: 2011-06-18

Published in Print: 2011-03-01


Citation Information: Biological Chemistry, Volume 392, Issue 3, Pages 217–221, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/bc.2011.003.

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