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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1988 Feb;85(4):1223–1226. doi: 10.1073/pnas.85.4.1223

Receptor-mediated rapid action of 1 alpha,25-dihydroxycholecalciferol: increase of intracellular cGMP in human skin fibroblasts.

J Barsony 1, S J Marx 1
PMCID: PMC279739  PMID: 2829219

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baran D. T., Milne M. L. 1,25 Dihydroxyvitamin D increases hepatocyte cytosolic calcium levels. A potential regulator of vitamin D-25-hydroxylase. J Clin Invest. 1986 May;77(5):1622–1626. doi: 10.1172/JCI112478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cloix J. F., Ulmann A., Monet J. D., Funck-Brentano J. L. Human parathyroid gland adenylate cyclase activity: inhibition by 24,25-dihydroxycholecalciferol in vitro. Clin Sci (Lond) 1981 Mar;60(3):339–341. doi: 10.1042/cs0600339. [DOI] [PubMed] [Google Scholar]
  3. Cloix J. F., d'Herbigny E., Ulmann A. Renal parathyroid hormone-dependent adenylate cyclase in vitamin D-deficient rats. Inhibition by hydroxylated vitamin D3 metabolites. J Biol Chem. 1980 Dec 10;255(23):11280–11283. [PubMed] [Google Scholar]
  4. Dufy B., Vincent J. D., Fleury H., Du Pasquier P., Gourdji D., Tixier-Vidal A. Membrane effects of thyrotropin-releasing hormone and estrogen shown by intracellular recording from pituitary cells. Science. 1979 May 4;204(4392):509–511. doi: 10.1126/science.107590. [DOI] [PubMed] [Google Scholar]
  5. Duval D., Durant S., Homo-Delarche F. Non-genomic effects of steroids. Interactions of steroid molecules with membrane structures and functions. Biochim Biophys Acta. 1983 Aug 11;737(3-4):409–442. doi: 10.1016/0304-4157(83)90008-4. [DOI] [PubMed] [Google Scholar]
  6. Edelman A., Garabedian M., Anagnostopoulos T. Mechanisms of 1,25(OH)2D3-induced rapid changes of membrane potential in proximal tubule: role of Ca2+-dependent K+ channels. J Membr Biol. 1986;90(2):137–143. doi: 10.1007/BF01869931. [DOI] [PubMed] [Google Scholar]
  7. Gamblin G. T., Liberman U. A., Eil C., Downs R. W., Jr, DeGrange D. A., Marx S. J. Vitamin D-dependent rickets type II. Defective induction of 25-hydroxyvitamin D3-24-hydroxylase by 1,25-dihydroxyvitamin D3 in cultured skin fibroblasts. J Clin Invest. 1985 Mar;75(3):954–960. doi: 10.1172/JCI111796. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Guillemant J., Guillemant S. Early rise in cyclic GMP after 1,25-dihydroxycholecalciferol administration in the chick intestinal mucosa. Biochem Biophys Res Commun. 1980 Apr 14;93(3):906–911. doi: 10.1016/0006-291x(80)91161-4. [DOI] [PubMed] [Google Scholar]
  9. Karsenty G., Lacour B., Ulmann A., Pierandréi E., Drüeke T. Early effects of vitamin D metabolites on phosphate fluxes in isolated rat enterocytes. Am J Physiol. 1985 Jan;248(1 Pt 1):G40–G45. doi: 10.1152/ajpgi.1985.248.1.G40. [DOI] [PubMed] [Google Scholar]
  10. Kreutter D., Matsumoto T., Peckham R., Zawalich K., Wen W. H., Zolock D. T., Rasmussen H. The effect of essential fatty acid deficiency on the stimulation of intestinal calcium transport by 1,25-dihydroxyvitamin D3. J Biol Chem. 1983 Apr 25;258(8):4977–4981. [PubMed] [Google Scholar]
  11. Kurnik B. R., Huskey M., Hagerty D., Hruska K. A. Vitamin D metabolites stimulate phosphatidylcholine transfer to renal brush-border membranes. Biochim Biophys Acta. 1986 Jun 13;858(1):47–55. doi: 10.1016/0005-2736(86)90290-7. [DOI] [PubMed] [Google Scholar]
  12. Kurnik B. R., Huskey M., Hruska K. A. 1,25-Dihydroxycholecalciferol stimulates renal phosphate transport by directly altering membrane phosphatidylcholine composition. Biochim Biophys Acta. 1987 Jan 13;917(1):81–85. doi: 10.1016/0005-2760(87)90286-4. [DOI] [PubMed] [Google Scholar]
  13. Liberman U. A., Eil C., Marx S. J. Receptor-positive hereditary resistance to 1,25-dihydroxyvitamin D: chromatography of hormone-receptor complexes on deoxyribonucleic acid-cellulose shows two classes of mutation. J Clin Endocrinol Metab. 1986 Jan;62(1):122–126. doi: 10.1210/jcem-62-1-122. [DOI] [PubMed] [Google Scholar]
  14. Lieberherr M. Effects of vitamin D3 metabolites on cytosolic free calcium in confluent mouse osteoblasts. J Biol Chem. 1987 Sep 25;262(27):13168–13173. doi: 10.1515/9783110846713.769. [DOI] [PubMed] [Google Scholar]
  15. Majewska M. D., Harrison N. L., Schwartz R. D., Barker J. L., Paul S. M. Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science. 1986 May 23;232(4753):1004–1007. doi: 10.1126/science.2422758. [DOI] [PubMed] [Google Scholar]
  16. Matsumoto T., Fontaine O., Rasmussen H. Effect of 1,25-dihydroxyvitamin D3 on phospholipid metabolism in chick duodenal mucosal cell. Relationship to its mechanism of action. J Biol Chem. 1981 Apr 10;256(7):3354–3360. [PubMed] [Google Scholar]
  17. Nabekura J., Oomura Y., Minami T., Mizuno Y., Fukuda A. Mechanism of the rapid effect of 17 beta-estradiol on medial amygdala neurons. Science. 1986 Jul 11;233(4760):226–228. doi: 10.1126/science.3726531. [DOI] [PubMed] [Google Scholar]
  18. Nemere I., Norman A. W. Parathyroid hormone stimulates calcium transport in perfused duodena from normal chicks: comparison with the rapid (transcaltachic) effect of 1,25-dihydroxyvitamin D3. Endocrinology. 1986 Sep;119(3):1406–1408. doi: 10.1210/endo-119-3-1406. [DOI] [PubMed] [Google Scholar]
  19. Nemere I., Yoshimoto Y., Norman A. W. Calcium transport in perfused duodena from normal chicks: enhancement within fourteen minutes of exposure to 1,25-dihydroxyvitamin D3. Endocrinology. 1984 Oct;115(4):1476–1483. doi: 10.1210/endo-115-4-1476. [DOI] [PubMed] [Google Scholar]
  20. Oshima J., Watanabe M., Hirosumi J., Orimo H. 1,25(OH)2D3 increases cytosolic Ca++ concentration of osteoblastic cells, clone MC3T3-E1. Biochem Biophys Res Commun. 1987 Jun 15;145(2):956–960. doi: 10.1016/0006-291x(87)91058-8. [DOI] [PubMed] [Google Scholar]
  21. Vesely D. L., Hill D. E. Estrogens and progesterone increase fetal and maternal guanylate cyclase activity. Endocrinology. 1980 Dec;107(6):2104–2109. doi: 10.1210/endo-107-6-2104. [DOI] [PubMed] [Google Scholar]
  22. Vesely D. L., Juan D. Cation-dependent vitamin D activation of human renal cortical guanylate cyclase. Am J Physiol. 1984 Jan;246(1 Pt 1):E115–E120. doi: 10.1152/ajpendo.1984.246.1.E115. [DOI] [PubMed] [Google Scholar]
  23. Vesely D. L. On the mechanism of action of adrenocortical steroids: cortisol and aldosterone enhance guanylate cyclase activity. J Pharmacol Exp Ther. 1980 Sep;214(3):561–566. [PubMed] [Google Scholar]
  24. Vesely D. L. Testosterone and its precursors and metabolites enhance guanylate cyclase activity. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3491–3494. doi: 10.1073/pnas.76.7.3491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Whalen R. E., Lauber A. H. Progesterone substitutes: cGMP mediation. Neurosci Biobehav Rev. 1986 Spring;10(1):47–53. doi: 10.1016/0149-7634(86)90032-1. [DOI] [PubMed] [Google Scholar]
  26. Yoshimoto Y., Nemere I., Norman A. W. Hypercalcemia inhibits the rapid stimulatory effect on calcium transport in perfused duodena from normal chicks mediated in vitro by 1,25-dihydroxyvitamin D3. Endocrinology. 1986 Jun;118(6):2300–2304. doi: 10.1210/endo-118-6-2300. [DOI] [PubMed] [Google Scholar]

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