ah-23848 and Alopecia

Previously, we found that orally administered soymetide-4 (MITL), an immunostimulating peptide derived from soybean beta-conglycinin alpha' subunit, suppressed alopecia induced by the anti-cancer drug etoposide in neonatal rats. Soymetide-4 has weak affinity for N-formyl-methionyl-leucyl-phenylalanine (fMLP) receptor. fMLP showed an anti-alopecia effect after intraperitoneal administration, though it was inactive after oral administration. Anti-alopecia effect of fMLP was blocked by pyrilamine or cimetidine, antagonists for histamine H1 or H2 receptor, respectively. However, the anti-alopecia effect of soymetide-4 was not inhibited by the histamine antagonists but by indomethacin, an inhibitor of cyclooxygenase (COX), or AH-23848B, an antagonist of the EP4 receptor for PGE2. Anti-alopecia effect of soymetide-4 was also blocked by pyrrolidine dithiocarbamate, an inhibitor of nuclear factor-kappaB (NF-kappaB). These results suggest that PGE2, which is produced after activation of COX by soymetide-4, might suppress apoptosis of hair matrix cells and etoposide-induced alopecia by activating NF-kappaB.

Topics: Adjuvants, Immunologic; Administration, Oral; Alopecia; Animals; Antigens, Plant; Antineoplastic Agents, Phytogenic; Biphenyl Compounds; Cyclooxygenase Inhibitors; Etoposide; Female; Globulins; Histamine H1 Antagonists; Indomethacin; Male; N-Formylmethionine Leucyl-Phenylalanine; NF-kappa B; Peptide Fragments; Prostaglandin-Endoperoxide Synthases; Pyrrolidines; Rats; Receptors, Formyl Peptide; Receptors, Prostaglandin E; Receptors, Prostaglandin E, EP4 Subtype; Seed Storage Proteins; Soybean Proteins; Thiocarbamates