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

Biosci Biotechnol Biochem. 2007 May;71(5):1198-202. doi: 10.1271/bbb.60656. Epub 2007 May 7.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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