Receptor-mediated rapid action of 1 alpha,25-dihydroxycholecalciferol: increase of intracellular cGMP in human skin fibroblasts.
AUTOR(ES)
Barsony, J
RESUMO
The intracellular cGMP concentration in normal human cultured fibroblasts was increased 2- to 3-fold by 1 alpha,25-dihydroxycholecalciferol [1 alpha,25-(OH)2D3] in a dose-dependent manner between 0.01 nM and 1 microM. The response was detectable within 1 min, reached a maximum (225% +/- 8% of baseline) at 6-8 min, and was no longer detectable at 30 min. The half-maximal effect of 1 alpha,25-(OH)2D3 was at 1.8 nM, and 24,25-dihydroxycholecalciferol showed an estimated EC50 100-fold higher. 1 beta,25-Dihydroxycholecalciferol, 25-hydroxycholecalciferol, and cholecalciferol had no detectable effect. Human skin fibroblasts with three different types of 1 alpha,25-(OH)2D3 receptor defect did not respond to 1 alpha,25-(OH)2D3 exposure with cGMP increase; however, the same cells (like normal cells) responded to testosterone or sodium nitroprusside with a rapid rise of cGMP. We conclude that the rapid rise of cGMP in response to calciferols shows an EC50 for 1 alpha,25-(OH)2D3, a cholecalciferol analog specificity, and a cell line dependency that are all suggestive of mediation through a specific 1 alpha,25-(OH)2D3 receptor.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=279739Documentos Relacionados
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