Chemotactic factor binding by metastatic tumour cells: evidence for a formyl-peptide receptor on a non-myelogenous cell

Analysis of fMet-Leu-[3H]Phe binding to Walker 256 carcinosarcoma cells demonstrated both saturable and reversible binding, and indicated the presence of a single population of binding sites having an equilibrium dissociation constant: KD = 15.7 +/− 3.3 X 10(−9) M, and with 2425 +/− 204 binding sites per cell. The specificity of the binding site was investigated by competitive inhibition of fMet-Leu-[3H]Phe binding studies using 10 oligoformyl peptides. These results demonstrated an order of peptide reactivity with marked similarity in specificity to the leucocyte binding sites for the formyl-peptides. The most active peptides also had potent agonist activity as determined by their ability to increase the cells' adherence response to nylon-wool fibres. In addition, a competitive antagonist of the formyl-peptide receptor, tert-butoxy-Phe-Leu-Phe-Leu-Phe, completely abolished the adherence response induced by fMet-Leu-Phe, but had no inhibitory effect on the adherence response caused by the tumour-promoting agent, phorbol myristate acetate. These data demonstrate that formyl-peptide receptors may be more common than we have anticipated and may be found on cells not derived from the myeloid series. Furthermore, these studies advance our understanding of stimulus-coupled responses in tumour cells.

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A Ganoderma-Derived Compound Exerts Inhibitory Effect Through Formyl Peptide Receptor 2

Frontiers in Pharmacology ◽

10.3389/fphar.2020.00337 ◽

2020 ◽

Vol 11 ◽

Author(s):

Huirong Wang ◽

Xingrong Peng ◽

Yunjun Ge ◽

Shuo Zhang ◽

Zhenyi Wang ◽

...

Keyword(s):

Inhibitory Effect ◽

Formyl Peptide Receptor ◽

Peptide Receptor ◽

Formyl Peptide

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Cyclosporine promotes glomerular endothelin binding in vivo.

Journal of the American Society of Nephrology ◽

10.1681/asn.v1111253 ◽

1991 ◽

Vol 1 (11) ◽

pp. 1253-1258

Author(s):

M Awazu ◽

M Sugiura ◽

T Inagami ◽

I Ichikawa ◽

V Kon

Keyword(s):

Binding Sites ◽

Competitive Inhibition ◽

Hepatic Tissue ◽

Binding Studies ◽

Endothelin 1 ◽

A Value ◽

Equilibrium Dissociation ◽

And Control ◽

Dissociation Constant Kd

It has previously been shown that administration of cyclosporine causes a prompt (within 15 min after infusion) increase in circulating level of endothelin 1 and a pattern of glomerular hypoperfusion and hypofiltration which can be ameliorated with antiendothelin antibody. We now show that 60 min after cyclosporine, serum endothelin 1 level falls to less than 2.55 +/- 0.31 pg/mL (N = 6), a value comparable to that found in normal animals (less than 2 pg/mL). The study presented here also examines whether sustained cyclosporine-induced glomerular dysfunction is associated with altered endothelin receptor characteristics. Saturation and competitive inhibition binding studies in isolated glomerular membranes showed two binding sites. Of these, the density of the low-affinity site was affected by cyclosporine treatment (851 +/- 117 versus 425 +/- 61 fmol/mg of protein; P less than 0.05; N = 6) without a change in equilibrium dissociation constant, KD. The high-affinity site was not affected. The receptor characteristics of another vasoconstrictor, angiotensin II, were not affected by cyclosporine. In addition, there was no difference in endothelin binding sites in hepatic tissue between cyclosporine and control rats. These results raise the intriguing possibility that cyclosporine-induced glomerular dysfunction involves upregulation of endothelin binding sites and that altered endothelin receptors appear specific to the kidney.

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Extensive Contact between Gi2 and N-Formyl Peptide Receptor of Human Neutrophils: Mapping of Binding Sites Using Receptor-Mimetic Peptides

Biochemistry ◽

10.1021/bi00020a017 ◽

1995 ◽

Vol 34 (20) ◽

pp. 6720-6728 ◽

Cited By ~ 28

Author(s):

Rajani K. Bommakanti ◽

Edward A. Dratz ◽

Daniel W. Siemsen ◽

Algirdas J. Jesaitis

Keyword(s):

Binding Sites ◽

Formyl Peptide Receptor ◽

Human Neutrophils ◽

Peptide Receptor ◽

Mimetic Peptides ◽

Formyl Peptide

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Antiflammin-2 Activates the Human Formyl-Peptide Receptor Like 1

The Scientific World JOURNAL ◽

10.1100/tsw.2006.247 ◽

2006 ◽

Vol 6 ◽

pp. 1375-1384 ◽

Cited By ~ 14

Author(s):

Ahmad M. Kamal ◽

Richard P.G. Hayhoe ◽

Anbalakan Paramasivam ◽

Dianne Cooper ◽

Roderick J. Flower ◽

...

Keyword(s):

Receptor Activation ◽

Inhibitory Effect ◽

Formyl Peptide Receptor ◽

Annexin A1 ◽

Hek 293 ◽

Peptide Receptor ◽

293 Cells ◽

Formyl Peptide ◽

Anti Inflammatory ◽

Extracellular Regulated Kinase

The anti-inflammatory actions of the nonapeptide antiflammin-2, identified by homology with uteroglobin and annexin-A1 sequences, have been described in some detail, yet its mechanisms of action remain elusive. Since recent data indicate an involvement of the formyl peptide receptor (FPR)-like 1 (or FPRL-1) in the effects of annexin-A1, we have tested here the effect of antiflammin-2 with respect to this receptor family. Using HEK-293 cells expressing either human FPR and FPRL-1, and an annexin-A1 peptide as tracer ([125I-Tyr]-Ac2-26), we found that antiflammin-2 competed for binding only at FPRL-1, and not FPR, with an approximate EC50of 1 μM. In line with data produced for the full-length protein, genuine receptor activation by antiflammin-2 was confirmed by rapid phosphorylation of extracellular-regulated kinase 1 and 2. Finally, study of the neutrophil interaction with activated endothelium under flow demonstrated an inhibitory effect of antiflammin-2, thus providing functional support to a role for the antiflammin-2/FPRL-1 anti-inflammatory axis.

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Paeonol Inhibits the Development of Rheumatoid Arthritis Through the Formyl Peptide Receptor 2

10.21203/rs.3.rs-727275/v1 ◽

2021 ◽

Author(s):

shao yubao ◽

Ji Dan ◽

Bao Lanxin ◽

Li Wenhao ◽

Dai Jinchen ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Autoimmune Disease ◽

Inhibitory Effect ◽

Formyl Peptide Receptor ◽

Inflammatory Factors ◽

Systemic Autoimmune Disease ◽

Data Sets ◽

Peptide Receptor ◽

Formyl Peptide ◽

Key Genes

Abstract Rheumatoid arthritis (RA) is a refractory systemic autoimmune disease associated with synovial inflammation. Previous studies postulate that paeonol has good anti-arthritis effects on RA. However, its systematic description remains unknown. Herein, we used bioinformatics tools to evaluate the mechanism of paeonol in arthritis systematically. A macrophage model was employed to study the differentially expressed genes between the inflammation and normal group, revealing 169 inflammation-related genes. Another 275 key genes affected by paeonol were identified in the same model. Three key genes, FPR2, Cd83, and Cfb, were obtained after combining the two data sets. Paeonol inhibited the release of inflammatory factors and the proliferation of synovial. However, its inhibitory effect was blocked by Fpr2 blocker WRW4. In summary, paeonol can inhibit the development of arthritis through FPR2. This provides new scope for the design and development of FPR2 ligands.

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