Leukotriene B4-induced human melanocyte pigmentation and leukotriene C4-induced human melanocyte growth are inhibited by different isoquinolinesulfonamides.
Leukotriene C4 (LTC4) is known to be a potent mitogen for cultured human neonatal melanocytes. We now demonstrate that leukotriene B4 (LTB4) can induce pigmentation in cultured human neonatal melanocytes in a dose-dependent fashion. The LTC4-induced mitogenesis is blocked by the cyclic nucleotide-dependent kinase inhibitor N-[2-(methyl-amino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H8). The LTB4-induced pigmentation is blocked by the protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7). We propose that LTB4-induced pigmentation and LTC4-induced mitogenesis are important in vivo signals. Their different effects in our culture system are blocked by different protein kinase inhibitors.
Morelli
J G
JG
Department of Dermatology, University of Colorado School of Medicine, Denver 80262.
Hake
S S
SS
Murphy
R C
RC
Norris
D A
DA
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000494:pharmacology*; D008544:Melanocytes / Q000187:drug effects*; D010858:Pigmentation / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013189:SRS-A / Q000494:pharmacology*
D007546:Isoquinolines; D010879:Piperazines; D013189:SRS-A; D007975:Leukotriene B4; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; D011493:Protein Kinase C