Cyclosporin H, Boc-MLF and Boc-FLFLF are antagonists that preferentially inhibit activity triggered through the formyl peptide receptor.
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 microM. 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.
Stenfeldt
Anna-Lena
AL
Department of Rheumatology and Inflammation Research, Guldhedsgatan 10, S 413 46, Göteborg, Sweden. anna-lena.stenfeldt@microbio.gu.se
Karlsson
Jennie
J
Wennerås
Christine
C
Bylund
Johan
J
Fu
Huamei
H
Dahlgren
Claes
C
D015936:Complement C5a / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D019255:NADPH Oxidases / Q000378:metabolism; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D044042:Receptors, Formyl Peptide / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000378:metabolism; D044067:Receptors, Lipoxin / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
C105101:FPR2 protein, human; D009842:Oligopeptides; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; C113617:Trp-Lys-Tyr-Met-Val-Met; C509690:tryptophyl-arginyl-tryptophyl-tryptophyl-tryptophyl-tryptophanamide; C081709:tert-butyloxycarbonyl-phenylalanyl-leucyl-phenylalanyl-leucyl-phenylalanyl-OH; D009240:N-Formylmethionine Leucyl-Phenylalanine; C046832:t-butyloxycarbonyl-methionyl-leucyl-phenylalanine; D015936:Complement C5a; D016572:Cyclosporine; D019255:NADPH Oxidases; C050025:cyclosporin H