Rapid action of 1,25-dihydroxyvitamin D3 on hepatocyte phospholipids

J Bone Miner Res. 1988 Dec;3(6):593-600. doi: 10.1002/jbmr.5650030603.

Abstract

Recent studies have reported cellular effects of 1,25-dihydroxyvitamin D3 within 15 minutes, a time period too rapid to be mediated by nuclear activation. The vitamin increases hepatocyte cytosolic calcium levels in the absence of extracellular calcium within 5 minutes. Since metabolites of phosphatidylinositol have been implicated as second messengers in the regulation of cytosolic calcium, we examined the effect of 1,25-dihydroxyvitamin D3 on hepatocyte phosphatidylinositol turnover and compared these effects to those produced by vasopressin. In isolated hepatocytes labeled with [3H]inositol, 1,25-dihydroxyvitamin D3 (4 nM) increased [3H]glycerophosphorylinositol by 16% (p less than 0.01) within 2.5 minutes, by 18% (p less than 0.01) after 5 minutes, and by 11% (p less than 0.05) after 10 minutes. At a concentration of 20 nM, 1,25-dihydroxyvitamin D3 increased [3H]glycerophosphorylinositol by 27% (p less than 0.01) after 5 minutes. Vitamin D did not affect [3H]inositol polyphosphates. Conversely, vasopressin had no effect on [3H]glycerophosphorylinositol but significantly increased [3H]inositol phosphate, [3H]inositol bisphosphate, and [3H]inositol triphosphate. 1,25-Dihydroxyvitamin D3 (4 nM) decreased [3H]phosphatidylinositol by 10% (p less than 0.05) after 5 minutes and by 16% (p less than 0.01) after 10 minutes. At a concentration of 20 nM, 1,25-dihydroxyvitamin D decreased [3H]phosphatidylinositol by 18% (p less than 0.01) after 5 minutes. The vitamin did not affect [3H]phosphatidylinositol bisphosphate or [3H]phosphatidylinositol trisphosphate. 24,25-Dihydroxyvitamin D had no effect on inositol phospholipids. The effects of 1,25-dihydroxyvitamin D3 on inositol phospholipids were blocked by quinacrine. Bromophenacylbromide inhibited the effects of 1,25-dihydroxyvitamin D3 on inositol phospholipids and also blocked the vitamin-induced increments in cytosolic calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcitriol / pharmacology*
  • Calcium / analysis
  • Chromatography, Ion Exchange
  • Esterification
  • In Vitro Techniques
  • Isoelectric Point
  • Liver / enzymology
  • Liver / metabolism*
  • Male
  • Phosphatidylinositols / metabolism*
  • Phospholipases / metabolism*
  • Phospholipases A / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Solubility
  • Vasopressins / pharmacology

Substances

  • Phosphatidylinositols
  • Vasopressins
  • Phospholipases
  • Phospholipases A
  • Calcitriol
  • Calcium