title: Receptor-mediated rapid action of 1 alpha,25-dihydroxycholecalciferol: increase of intracellular cGMP in human skin fibroblasts.
abstract: 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.
authors.affiliation: Mineral Metabolism Section, National Institute of Diabetes, Digestive, and Kidney Diseases, Bethesda, MD 20892.
authors.forename: J
authors.initials: J
authors.lastname: Barsony
authors.forename: S J
authors.initials: SJ
authors.lastname: Marx
mesh_terms: D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology; D006152:Cyclic GMP / Q000096:biosynthesis*; D013196:Dihydrotestosterone / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000187:drug effects / Q000378:metabolism*; D012867:Skin; D013268:Stimulation, Chemical; D013739:Testosterone / Q000494:pharmacology
chemical_list: D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D013196:Dihydrotestosterone; D002762:Cholecalciferol; D013739:Testosterone; D002117:Calcitriol; D006152:Cyclic GMP