Mechanism of the protective effect of intraperitoneally administered agonists for formyl peptide receptors against chemotherapy-induced alopecia.

Abstract

Previously, we found that an intraperitoneally administered chemotactic peptide, N-formyl-Met-Leu-Phe (fMLP), and MMK-1, a selective agonist of formyl peptide receptor-like 1 (FPRL1) receptor, the low affinity subtype of the fMLP receptor, prevented the alopecia in neonatal rats induced by the anticancer agent etoposide. The anti-alopecia effect of fMLP was not inhibited at all by Boc-FLFLF, a selective antagonist of formylpeptide receptor (FPR), which is the high affinity subtype of the fMLP receptor, but it was partly inhibited by Trp-Arg-Trp-Trp-Trp-Trp-NH(2) (WRW(4)), an antagonist of FPRL1 receptor. On the other hand, the anti-alopecia effect of MMK-1 was completely abolished by WRW(4). The anti-alopecia effects of fMLP and MMK-1 were also inhibited by Lys-D-Pro-Thr (K(D)PT) and pyrrolidine dithiocarbamate, which are inhibitors of interleukin-1 (IL-1) and nuclear factor-kappaB (NF-kappaB) respectively. Hence, we suggest that the anti-alopecia mechanisms of intraperitoneally administered fMLP and MMK-1 include activation of NF-kappaB via IL-1 release downstream of the FPRL1 receptor homolog in rats.

• Authors: Takahiro Tsuruki, Kyoya Takahata, Masaaki Yoshikawa
• Journal: Bioscience, biotechnology, and biochemistry (Biosci Biotechnol Biochem) Vol. 71 Issue 5 Pg. 1198-202 (May 2007) ISSN: 0916-8451 [Print] England
• PMID: 17485829 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MMK-1 peptide
• Peptides
• Receptors, Formyl Peptide
• N-Formylmethionine Leucyl-Phenylalanine
• Etoposide

Topics

• Alopecia (chemically induced, drug therapy)
• Animals
• Etoposide (toxicity)
• Female
• Injections, Intraperitoneal
• Male
• N-Formylmethionine Leucyl-Phenylalanine (administration & dosage, pharmacology)
• Peptides (administration & dosage, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Formyl Peptide (agonists)