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The peptidomimetic Lau-(Lys-βNSpe)6-NH2 antagonizes formyl peptide receptor 2 expressed in mouse neutrophils.

Författare och institution:
Sarah Line Skovbakke (-); Malene Winther (Institutionen för medicin); Michael Gabl (Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning); André Holdfeldt (Institutionen för medicin); Sara K. Lindén (Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi); Ji Ming Wang (-); Claes Dahlgren (Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning); Henrik Franzyk (-); Huamei Forsman (Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning)
Publicerad i:
Biochemical pharmacology,
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
The formyl peptide receptor (FPR) gene family has a complex evolutionary history and comprises eight murine members but only three human representatives. To enable translation of results obtained in mouse models of human diseases, more comprehensive knowledge of the pharmacological similarities/differences between the human and murine FPR family members is required. Compared to FPR1 and FPR2 expressed by human neutrophils, very little is known about agonist/antagonist recognition patterns for their murine orthologues, but now we have identified two potent and selective formylated peptide agonists (fMIFL and PSMα2) for Fpr1 and Fpr2, respectively. These peptides were used to determine the inhibition profile of a set of antagonists with known specificities for the two FPRs in relation to the corresponding murine receptors. Some of the most potent and selective antagonists for the human receptors proved to be devoid of effect on their murine orthologues as determined by their inability to inhibit superoxide release from murine neutrophils upon stimulation with receptor-specific agonists. The Boc-FLFLF peptide was found to be a selective antagonist for Fpr1, whereas the lipidated peptidomimetic Lau-(Lys-βNSpe)6-NH2 and the hexapeptide WRW4 were identified as Fpr2-selective antagonists.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Medicinska grundvetenskaper
Postens nummer:
Posten skapad:
2016-09-11 10:50

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