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.

[1]  G. Brooks,et al.  Protein kinase C down-regulation, and not transient activation, correlates with melanocyte growth. , 1991, Cancer research.

[2]  R. Murphy,et al.  Leukotrienes C4 and D4 as potent mitogens for cultured human neonatal melanocytes. , 1989, The Journal of investigative dermatology.

[3]  B. Gilchrest,et al.  Human melanogenesis is stimulated by diacylglycerol. , 1989, The Journal of investigative dermatology.

[4]  J. Habener,et al.  Distinct adenosine 3',5'-monophosphate and phorbol ester-responsive signal transduction pathways converge at the level of transcriptional activation by the interactions of DNA-binding proteins. , 1989, Molecular endocrinology.

[5]  B. Gilchrest,et al.  Regulation of human melanocyte growth, dendricity, and melanization by keratinocyte derived factors. , 1989, The Journal of investigative dermatology.

[6]  M. Herlyn,et al.  Regulatory factors that determine growth and phenotype of normal human melanocytes. , 1988, Experimental cell research.

[7]  R. Halaban,et al.  Basic fibroblast growth factor from human keratinocytes is a natural mitogen for melanocytes , 1988, The Journal of cell biology.

[8]  B. Gilchrest,et al.  Ultraviolet radiation directly induces pigment production by cultured human melanocytes , 1987, Journal of cellular physiology.

[9]  H. Tagami,et al.  Stimulatory effect of prostaglandin E2 on the configuration of normal human melanocytes in vitro. , 1987, The Journal of investigative dermatology.

[10]  B. Gilchrest,et al.  Relative responsiveness of cultured human epidermal melanocytes and melanoma cells to selected mitogens. , 1986, The Journal of investigative dermatology.

[11]  J. Nordlund,et al.  Prostaglandin E2 and D2 but not MSH stimulate the proliferation of pigment cells in the pinnal epidermis of the DBA/2 mouse. , 1986, The Journal of investigative dermatology.

[12]  S. Kawamoto,et al.  Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C. , 1984, Biochemistry.

[13]  E. Rozengurt,et al.  Disappearance of Ca2+-sensitive, phospholipid-dependent protein kinase activity in phorbol ester-treated 3T3 cells. , 1984, Biochemical and biophysical research communications.

[14]  J. Voorhees,et al.  Arachidonic acid and leukotrienes in dermatology. , 1983, The Journal of investigative dermatology.

[15]  J. Voorhees.  Leukotrienes and other lipoxygenase products in the pathogenesis and therapy of psoriasis and other dermatoses. , 1983, Archives of dermatology.

[16]  M. Eisinger,et al.  Selective proliferation of normal human melanocytes in vitro in the presence of phorbol ester and cholera toxin. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Y. Kitano.  Effects of dibutyryl adenosine 3',5'-cyclic monophosphate on human melanocytes in vitro. , 1976, Acta dermato-venereologica.