The inositol-1,4,5-trisphosphate system is involved in rapid effects of aldosterone in human mononuclear leukocytes

J Clin Endocrinol Metab. 1993 Dec;77(6):1452-7. doi: 10.1210/jcem.77.6.8263127.


There is increasing evidence for rapid steroid action on electrolyte transport in human mononuclear leukocytes (HML). In HML, aldosterone stimulates the Na+/H+ antiporter within a few minutes. Because a variety of hormones and growth factors activate the Na+/H+ antiporter via protein kinase C and inositol phospholipids, a possible involvement of inositol-1,4,5-trisphosphate (IP3) in the rapid effects of aldosterone in HML was investigated. The stimulation of IP3 generation was started by the addition of aldosterone, concanavalin A, or other steroids. A significant increase in IP3 levels by aldosterone (1 nmol/L, P < 0.05) was found after 1 min, similar to that found after concanavalin A (25 micrograms/mL). Aldosterone caused a concentration-dependent elevation of IP3 levels, with an apparent EC50 of approximately 0.1 nmol/L. Fludrocortisone stimulated IP3 generation at similar concentrations, whereas a weaker IP3 stimulation by glucocorticoids (hydrocortisone, dexamethasone) occurred at micromolar concentrations only. Canrenone, a potent inhibitor of classical aldosterone action, was not effective up to a concentration of 100 nmol/L. These findings show kinetic and pharmacological similarities with both the functional data on Na+/H+ antiport stimulation by aldosterone and the studies of 125I-aldosterone binding to plasma membranes of HML. Thus, these data are the first to indicate an involvement of the phosphoinositide pathway in the rapid membrane effects of aldosterone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aldosterone / pharmacology*
  • Calcium / metabolism
  • Canrenone / pharmacology
  • Concanavalin A / pharmacology
  • Humans
  • Hydrocortisone / pharmacology
  • Inositol 1,4,5-Trisphosphate / biosynthesis*
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Sodium-Hydrogen Exchangers / drug effects
  • Terpenes / pharmacology
  • Thapsigargin


  • Sodium-Hydrogen Exchangers
  • Terpenes
  • Concanavalin A
  • Aldosterone
  • Thapsigargin
  • Canrenone
  • Inositol 1,4,5-Trisphosphate
  • Calcium
  • Hydrocortisone