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Orally administered FPRL1 receptor agonist peptide MMK-1 inhibits etoposide-induced alopecia by a mechanism different from intraperitoneally administered MMK-1.

Abstract
Oral administration for 6 days of 100 mg/kg MMK-1, an agonist peptide selective for the FPRL1 receptor, suppressed alopecia induced by the anticancer drug etoposide in neonatal rats. The anti-alopecia effect of orally administered MMK-1 was not inhibited by pyrilamine or cimetidine, antagonists for histamine H1 and H2 receptors, respectively, which blocked the anti-alopecia effect of intraperitoneally administered MMK-1 at a dose of 10 mg/kg for 4 days. However, the anti-alopecia effect of orally administered MMK-1 was inhibited by indomethacin, an inhibitor of cyclooxygenase (COX), or AH-23848B, an antagonist of the EP4 receptor for prostaglandin (PG) E2, suggesting involvement of PGE2 release and the EP4 receptor in the oral MMK-1 anti-alopecia mechanism. The anti-alopecia effect of orally administered MMK-1 was also blocked by an inhibitor of nuclear factor-kappaB (NF-kappaB), pyrrolidine dithiocarbamate, suggesting that the oral anti-alopecia effect of MMK-1 may be mediated by activation of NF-kappaB. These results suggest that MMK-1 bound to FPRL1 receptor might suppress etoposide-induced apoptosis of hair follicle cells and alopecia by way of PGE2 release and NF-kappaB activation.
AuthorsTakahiro Tsuruki, Masaaki Yoshikawa
JournalPeptides (Peptides) Vol. 27 Issue 4 Pg. 820-5 (Apr 2006) ISSN: 0196-9781 [Print] United States
PMID16183167 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • FPR2 protein, human
  • MMK-1 peptide
  • Peptides
  • Receptors, Formyl Peptide
  • Receptors, Lipoxin
  • Etoposide
  • Cimetidine
  • Pyrilamine
  • Indomethacin
Topics
  • Administration, Oral
  • Alopecia (chemically induced, drug therapy)
  • Animals
  • Cimetidine (pharmacology)
  • Disease Models, Animal
  • Etoposide (pharmacology)
  • Female
  • Indomethacin (pharmacology)
  • Injections, Intraperitoneal
  • Male
  • Peptides (administration & dosage, pharmacology)
  • Pyrilamine (pharmacology)
  • Rats
  • Receptors, Formyl Peptide (agonists)
  • Receptors, Lipoxin (agonists)

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