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

Publisher Website
Google Scholar
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‐dihy‐droxyvitamin 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]glycerophosphoryIinositol by 16% (p < 0.01) within 2.5 minutes, by 18% (p < 0.01) after 5 minutes, and by 11% (p < 0.05) after 10 minutes. At a concentration of 20 nM, 1,25‐dihydroxyvitamin D3 increased [3H]glycerophosphorylinositol by 27% (p < 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 trisphosphate. 1,25‐Dihy‐droxyvitamin D3 (4 nM) decreased [3H]phosphatidylinositol by 10% (p < 0.05) after 5 minutes and by 16% (p < 0.01) after 10 minutes. At a concentration of 20 nM, 1,25‐dihydroxyvitamin D decreased [3H]phosphatidylinositol by 18% (p < 0.01) after 5 minutes. The vitamin did not affect [3H]phosphatidylinositol bis‐phosphate 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. In isolated hepatocytes labeled with [3H]arachidonic acid, 1,25‐dihydroxyvitamin D3 (20 nM) decreased 3H‐labeled phosphatidylcholine and phosphatidylethanolamine, as well as phosphatidylinositol. The data indicate that 1,25‐dihydroxyvitamin D3 may enhance deacylation of hepatocyte phospholipids, perhaps by activation of phospholipase A activity. The ability of vitamin D to increase cytosolic calcium requires activation of phospholipase A. Although both 1,25‐dihydroxyvitamin D and vasopressin rapidly affect phospholipid metabolism, their mechanisms of action differ.
Funding Information
  • NIH (DK 39085)

This publication has 32 references indexed in Scilit: