A truncated form of CKbeta8-1 is a potent agonist for human formyl peptide-receptor-like 1 receptor

Br J Pharmacol. 2004 Jan;141(1):37-46. doi: 10.1038/sj.bjp.0705592. Epub 2003 Dec 8.


1. Human formyl peptide-receptor-like-1 (FPRL-1) is a promiscuous G protein-coupled receptor (GPCR), and belongs to a chemoattractant receptor family protein. This receptor has been reported to interact with various host-derived peptides and lipids involved in inflammatory responses. We described here, a novel role for FPRL-1 as a high-affinity beta-chemokine receptor for an N-terminally truncated form of the CKbeta8 (CCL23/MPIF-1) splice variant CKbeta8-1 (22-137 aa). 2. RT-PCR analysis of mRNA derived from human tissues and cells revealed a predominant expression of FPRL-1 in inflammatory cells, particularly in neutrophils. 3. Intracellular calcium mobilisation assay, used as screening tool, in recombinant Chinese hamster ovary (CHO-K1) and human embryonic kidney (HEK293s) cells coexpressing FPRL-1 and Galpha(16), demonstrated FPRL-1 is a functional high-affinity receptor for CKbeta8-1 (46-137 aa, sCKbeta8-1), with pEC(50) values of 9.13 and 8.85, respectively. 4. The FPRL-1 activation in CHO-K1 cells is mediated by Galpha(i)/Galpha(o) proteins, as assessed by pertussis toxin sensitivity and inhibition of forskolin-induced cyclic AMP accumulation. 5. Binding experiments were performed with a radio-iodinated synthetic peptide, [(125-)I]-WKYMVm, a known potent FPRL-1 agonist. CHO-K1 cell membranes expressing FPRL-1 bound [(125-)I]-WKYMVm with a K(d) value of 9.34. Many known FPRL-1 agonists were tested and sCKbeta8-1 was the most effective nonsynthetic ligand in displacing the radiolabelled agonist, with a pIC(50) of 7.97. 6. The functional significance of sCKbeta8-1 interaction with FPRL-1 was further demonstrated by the activation of polymorphonuclear leukocytes (PMNs) calcium mobilisation and chemotaxis. These interactions were shown to be via FPRL-1 by specific blockade of PMNs activation in the presence of an FPRL-1 antibody.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CHO Cells
  • Calcium / metabolism
  • Cell Movement / drug effects
  • Chemokines, CC / chemistry*
  • Chemokines, CC / metabolism
  • Chemokines, CC / pharmacology*
  • Chemotaxis / drug effects
  • Cricetinae
  • Drug Evaluation, Preclinical / methods
  • Female
  • GTP-Binding Protein alpha Subunits, Gi-Go / chemistry
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
  • Gene Expression
  • Humans
  • Iodine Radioisotopes / metabolism
  • Kidney / cytology
  • Kidney / drug effects
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Polymerase Chain Reaction / methods
  • RNA, Messenger / genetics
  • Receptors, Formyl Peptide / drug effects*
  • Receptors, Formyl Peptide / genetics
  • Receptors, Formyl Peptide / metabolism
  • Receptors, G-Protein-Coupled
  • Receptors, Lipoxin / drug effects*
  • Receptors, Lipoxin / genetics
  • Receptors, Lipoxin / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction


  • CCL23 protein, human
  • Chemokines, CC
  • FPR2 protein, human
  • Iodine Radioisotopes
  • RNA, Messenger
  • Receptors, Formyl Peptide
  • Receptors, G-Protein-Coupled
  • Receptors, Lipoxin
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Calcium