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

Eric Grouzmann, Paul Bigliardi, Monique Appenzeller, André Pannatier, Thierry Buclin

Research output: Contribution to journalArticle

9 Scopus citations

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, doubleblind 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.

Original languageEnglish (US)
Pages (from-to)217-221
Number of pages5
JournalBiological Chemistry
Volume392
Issue number3
DOIs
StatePublished - Mar 1 2011

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Keywords

  • Clinical trial
  • Dipeptidylpeptidase IV
  • Flare
  • Proteases
  • Tachykinin
  • Wheal

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