Orally administered FPRL1 receptor agonist peptide MMK-1 inhibits etoposide-induced alopecia by a mechanism different from intraperitoneally administered MMK-1.
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.
Tsuruki
Takahiro
T
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan.
Yoshikawa
Masaaki
M
D000284:Administration, Oral; D000505:Alopecia / Q000139:chemically induced* / Q000188:drug therapy*; D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D004195:Disease Models, Animal; D005047:Etoposide / Q000494:pharmacology*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D010455:Peptides / Q000008:administration & dosage* / Q000494:pharmacology*; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D044042:Receptors, Formyl Peptide / Q000819:agonists*; D044067:Receptors, Lipoxin / Q000819:agonists*
C105101:FPR2 protein, human; C408903:MMK-1 peptide; D010455:Peptides; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; D005047:Etoposide; D002927:Cimetidine; D011738:Pyrilamine; D007213:Indomethacin