Decreasing extracellular Na+ concentration triggers inositol polyphosphate production and Ca2+ mobilization.
Removing extracellular Na+ (Na+o) evoked a large increase in cytosolic free Ca2+ concentration ([Ca2+]i in human skin fibroblasts. Decreasing [Na+]o from 120 to 14 mM caused the half-maximal peak increase in [Ca2+]i. Removing Na+o strongly stimulated 45Ca2+ efflux and decreased total cell Ca2+ by about 40%. Bradykinin caused changes in [Ca2+]i, total Ca2+, and 45Ca2+ fluxes similar to those evoked by removing Na+o. Prior stimulation of the cells with bradykinin prevented Na+o removal from increasing [Ca2+]i and vice versa. Na+o removal rapidly increased [3H]inositol polyphosphate production. Loading the cells with Na+ had no effect on the increase in 45Ca2+ efflux produced by Na+o removal. Therefore, decreasing [Na+]o probably stimulates a "receptor(s)" which is sensitive to extracellular, not intracellular, Na+. Removing Na+o also mobilized intracellular Ca2+ in smooth muscle and endothelial cells cultured from human umbilical and dog coronary arteries, respectively.
Smith
J B
JB
Department of Pharmacology, University of Alabama, Birmingham 35294.
Dwyer
S D
SD
Smith
L
L
D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000096:biosynthesis*; D007424:Intracellular Fluid / Q000378:metabolism; D007700:Kinetics; D012867:Skin / Q000378:metabolism; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology*; D013403:Sugar Phosphates / Q000096:biosynthesis*; D014316:Tritium
D002132:Calcium Radioisotopes; D007295:Inositol Phosphates; D013403:Sugar Phosphates; D014316:Tritium; D007294:Inositol; D012964:Sodium; D001920:Bradykinin; D002118:Calcium