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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
27
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pubmed:dateCreated |
1991-10-29
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pubmed:abstractText |
We demonstrate here that human melanocytes could be regulated by endothelin (ET) derivatives, potent vasoconstrictive peptides synthesized by endothelial cells, to stimulate their proliferation and melanization via a receptor-mediated signal transduction pathway. Receptor-binding assay using [125I]ET indicated that unlabeled ET-1 or ET-2 competitively inhibited each binding of labeled ETs to melanocytes with a concentration for half-maximal inhibition (IC50) of 0.7 or 0.9 nM, respectively. The dissociation constant (Kd) and the number of sites of the specific bindings of ET-1 and those of ET-2 were almost the same (Kd: 1.81 nM, binding sites: 7.0-8.0 x 10(4) per cell). Upon incubation with cultured cells, the mass contents of inositol 1,4,5-trisphosphate and intracellular calcium level were substantially increased by 10 nM ET-1, ET-2, and ET-3, but not by big-ET with maximal response at 80-130-s postincubation. The addition of ET-1 and ET-2 at 1-50 nM concentrations caused human melanocytes to significantly stimulate DNA [( 3H]thymidine incorporation) and melanin synthesis (3H2O release and [14C] thiouracil incorporation). Furthermore, ETs exhibited an additive stimulatory effect on basic fibroblast growth factor-stimulated DNA synthesis. In a long-term serum-free culture system, the strongest stimulation of growth by 10 nM ET-1 or ET-2 was observed in the presence of 10 nM cholera toxin and 0.2% bovine pituitary extract, resulting in a 4.5-fold increase in cell number for 12 culture days. These findings strongly suggest involvement of ET in the mechanism regulating proliferation and melanization of human melanocytes.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
266
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
18352-7
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:1917960-Binding, Competitive,
pubmed-meshheading:1917960-Cell Division,
pubmed-meshheading:1917960-Endothelins,
pubmed-meshheading:1917960-Fluorescent Dyes,
pubmed-meshheading:1917960-Fura-2,
pubmed-meshheading:1917960-Humans,
pubmed-meshheading:1917960-Melanocytes,
pubmed-meshheading:1917960-Monophenol Monooxygenase,
pubmed-meshheading:1917960-Signal Transduction
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pubmed:year |
1991
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pubmed:articleTitle |
Effects of endothelins on signal transduction and proliferation in human melanocytes.
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pubmed:affiliation |
Tochigi Research Laboratories, Kao Corporation, Japan.
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pubmed:publicationType |
Journal Article
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