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Cyclosporin H, Boc-MLF and Boc-FLFLF are Antagonists that Preferentially Inhibit Activity Triggered Through the Formyl Peptide Receptor

Journal article
Authors Anna-Lena Stenfeldt
Jennie Karlsson
Christine Wennerås
Johan Bylund
Huamei Fu
Claes Dahlgren
Published in Inflammation
Publication year 2007
Published at Institute of Medicine, Department of Rheumatology and Inflammation Research
Institute of Biomedicine, Department of Microbiology and Immunology
Institute of Biomedicine, Department of Infectious Medicine
Language en
Links www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Medical and Health Sciences, Microbiology in the medical area

Abstract

In order to properly interpret receptor inhibition experiments, the precise receptor specificities of the employed antagonists are of crucial importance. Lately, a great number of agonists for various formyl peptide receptors have been identified using a selection of antagonists. However, some confusion exists as to the precise receptor specificities of many of these antagonists. We have investigated the effects of formyl peptide receptor family antagonists on the neutrophil response induced by agonists for the formyl peptide receptor (FPR) and the formyl peptide receptor like 1 (FPRL1). To determine FPR- and FPRL1-specific interactions, these antagonists should not be used at used at concentrations above 10 muM. Signaling through FPR was inhibited by low concentrations of the antagonists cyclosporin H, Boc-MLF (also termed Boc-1), and Boc-FLFLFL (also termed Boc-2), while higher concentrations also partly inhibited the signaling through FPRL1. The antagonist WRWWWW (WRW(4)) specifically inhibited the signaling through FPRL1 at low concentrations but at high concentrations also partly the signaling through FPR. Based on the difference in potency of cyclosporin H and the two Boc-peptides, we suggest using cyclosporin H as a specific inhibitor for FPR. To specifically inhibit the FPRL1 response the antagonist WRW(4) should be used.

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