Thapsigargin increases cellular free calcium and intracellular sodium concentrations in cultured rat glomerular mesangial cells.
We examined whether thapsigargin increases cellular free calcium ([Ca2+]i) and intracellular sodium concentration ([Na+]i) in cultured rat glomerular mesangial cells. 1 x 10(-6) M Thapsigargin increased [Ca2+]i to 244.4 from 86.6 nM, an increase sustained at least during the 15 min observation period. Such an increase in [Ca2+]i was transient in Ca(2+)-free medium containing 1 x 10(-4) M EGTA. An increase in [Ca2+]i by thapsigargin was not altered by 1 x 10(-6) M nicardipine, a L-type Ca2+ channel blocker. Thapsigargin also produced a sustained rise in [Na+]i in a dose-dependent manner. However, preincubation of cells with Ca(2+)-free medium completely blocked the increase in [Na+]i by thapsigargin. These results indicate that thapsigargin increases [Ca2+]i by blocking endoplasmic Ca(2+)-ATPase and enhancing Ca2+ entry, and that the increased Ca2+ influx is triggering an increase in [Na+]i stimulated by thapsigargin per se in glomerular mesangial cells.
Ishikawa
S
S
Department of Medicine, Jichi Medical School, Tochigi, Japan.
Fujisawa
G
G
Okada
K
K
Saito
T
T
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D016232:Endothelins / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D013729:Terpenes / Q000494:pharmacology*; D019284:Thapsigargin; D013997:Time Factors
D016232:Endothelins; D013729:Terpenes; D001127:Arginine Vasopressin; D019284:Thapsigargin; D012964:Sodium; D000252:Calcium-Transporting ATPases; D002118:Calcium