title: The inositol-1,4,5-trisphosphate system is involved in rapid effects of aldosterone in human mononuclear leukocytes.
abstract: 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.
authors.affiliation: Medizinische Klinik, Klinikum Innenstadt, University of Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Christ
authors.forename: C
authors.initials: C
authors.lastname: Eisen
authors.forename: J
authors.initials: J
authors.lastname: Aktas
authors.forename: K
authors.initials: K
authors.lastname: Theisen
authors.forename: M
authors.initials: M
authors.lastname: Wehling
mesh_terms: D000328:Adult; D000450:Aldosterone / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002192:Canrenone / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017923:Sodium-Hydrogen Exchangers / Q000187:drug effects; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
chemical_list: D017923:Sodium-Hydrogen Exchangers; D013729:Terpenes; D003208:Concanavalin A; D000450:Aldosterone; D019284:Thapsigargin; D002192:Canrenone; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium; D006854:Hydrocortisone