Substance P-induced skin inflammation is not modulated by a single dose of sitagliptin in human volunteers
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Eric Grouzmann
,
Paul Bigliardi
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.
©2011 by Walter de Gruyter Berlin New York
Articles in the same Issue
- Guest Editorial
- Highlight: Dipeptidyl peptidase 4 and related proteins
- HIGHLIGHT: DIPEPTIDYL PEPTIDASE 4 AND RELATED PROTEINS
- Novel aspects of cellular action of dipeptidyl peptidase IV/CD26
- Outside or inside: role of the subcellular localization of DP4-like enzymes for substrate conversion and inhibitor effects
- Expression and spatial heterogeneity of dipeptidyl peptidases in endothelial cells of conduct vessels and capillaries
- Expression and role of the cell surface protease seprase/fibroblast activation protein-α (FAP-α) in astroglial tumors
- DPP-4 inhibition increases GIP and decreases GLP-1 incretin effects during intravenous glucose tolerance test in Wistar rats
- Substance P-induced skin inflammation is not modulated by a single dose of sitagliptin in human volunteers
- Selective inhibition of dipeptidyl peptidase 4 by targeting a substrate-specific secondary binding site
- PETIR-001, a dual inhibitor of dipeptidyl peptidase IV (DP IV) and aminopeptidase N (APN), ameliorates experimental autoimmune encephalomyelitis in SJL/J mice
- CELL BIOLOGY AND SIGNALING
- Identification and characterisation of novel Mss4-binding Rab GTPases
- Identification of lily pollen 14-3-3 isoforms and their subcellular and time-dependent expression profile
- PROTEOLYSIS
- Myeloperoxidase-catalyzed oxidative inactivation of human kininogens: the impairment of kinin-precursor and prekallikrein-binding functions
Articles in the same Issue
- Guest Editorial
- Highlight: Dipeptidyl peptidase 4 and related proteins
- HIGHLIGHT: DIPEPTIDYL PEPTIDASE 4 AND RELATED PROTEINS
- Novel aspects of cellular action of dipeptidyl peptidase IV/CD26
- Outside or inside: role of the subcellular localization of DP4-like enzymes for substrate conversion and inhibitor effects
- Expression and spatial heterogeneity of dipeptidyl peptidases in endothelial cells of conduct vessels and capillaries
- Expression and role of the cell surface protease seprase/fibroblast activation protein-α (FAP-α) in astroglial tumors
- DPP-4 inhibition increases GIP and decreases GLP-1 incretin effects during intravenous glucose tolerance test in Wistar rats
- Substance P-induced skin inflammation is not modulated by a single dose of sitagliptin in human volunteers
- Selective inhibition of dipeptidyl peptidase 4 by targeting a substrate-specific secondary binding site
- PETIR-001, a dual inhibitor of dipeptidyl peptidase IV (DP IV) and aminopeptidase N (APN), ameliorates experimental autoimmune encephalomyelitis in SJL/J mice
- CELL BIOLOGY AND SIGNALING
- Identification and characterisation of novel Mss4-binding Rab GTPases
- Identification of lily pollen 14-3-3 isoforms and their subcellular and time-dependent expression profile
- PROTEOLYSIS
- Myeloperoxidase-catalyzed oxidative inactivation of human kininogens: the impairment of kinin-precursor and prekallikrein-binding functions
