Substance P-induced skin inflammation is not modulated by a single dose of
sitagliptin in human volunteers.
Author(s): Grouzmann E, Bigliardi P, Appenzeller M, Pannatier A, Buclin T.
Affiliation(s): Division de Pharmacologie et Toxicologie Cliniques, CHU Vaudois, CH-1011
Lausanne, Switzerland. eric.grouzmann@chuv.ch
Publication date & source: 2011, Biol Chem. , 392(3):217-21
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.
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