The synthetic peptide Trp-Lys-Tyr-Met-Val-D-Met is a potent chemotactic agonist for mouse formyl peptide receptor

Formyl peptides are potent neutrophil chemoattractants. In humans and rabbi ts, the formyl peptide receptor (FPR) binds N-formyl-Met-Leu-Phe (fMLF) wit h high affinity (K-d approximate to 1 nM), The mouse FPR (mFPR) is a low-af finity receptor for fMLF (K-d approximate to 100 nM); therefore, other agon ists for this receptor may exist. Using mFPR-transfected rat basophilic leu kemia cells, we found that a recently identified synthetic peptide Trp-Lys- Tyr-Met-Val-D-Met (WKYMVm) is a potent agonist for mFPR, WKYMVm induced cal cium mobilization with an EC50 of 1.2-1.5 nM, Optimal chemotaxis was achiev ed with I nM of WKYMVm, but it required 100 nM of fMLF. WKYMVm stimulated r apid and potent phosphorylation of the mitogen-activated protein kinases ex tracellular signal-related kinases 1 and 2 when used at 50 nM, Pertussis to xin only partially blocked calcium mobilization and production of inositol I,4,5-trisphosphate in the stimulated mFPR cells, suggesting the possibilit y that this receptor couples to G alpha proteins other than Gi and Go. Comp etitive binding and desensitization data suggest that both peptides interac t with the same receptor but may use nonoverlapping binding sites because W KYMVm was unable to effectively displace [H-3]fMLF bound to mFPR, These res ults provide evidence for the presence of an alternative potent agonist for mFPR, and suggest a potential usage of WKYMVm for probing the ligand-recep tor interactions with the murine formyl peptide receptor homologs.