Na(+)/Ca(2+) exchange inhibitors modulate thapsigargin-induced Ca(2+) and Na(+) influx in human lymphocytes.
Thapsigargin has been shown the elevate intracellular Na(+) concentration in human lymphocytes, but mechanisms underlying thapsigargin-induced Na(+) entry are little understood. In the present study we investigated thapsigargin-induced changes in cytosolic free Na(+) and Ca(2+) concentration in human lymphocytes after inhibition of the Na(+)/Ca(2+) exchange with two structurally unrelated compounds, dimethylthiourea ad bepridil. The intracellular Na(+) increase induced by 5 microM thapsigargin was significantly enhanced in the presence of 5 mM dimethylthiourea or 40 microM bepridil. In contrast, both compounds significantly decreased the thapsigargin-induced intracellular Ca(2+) elevation. No effect of dimethylthiourea or bepridil on thapsigargin-induced Ca(2+) influx was observed in the absence of extracellular Na(+). These observations are consistent with the hypothesis that thapsigargin stimulates Na(+)/Ca(2+ )exchange in human lymphocytes. However, Na(+)/Ca(2+) exchange does not mediate Na(+) influx in human lymphocytes.
Nofer
J R
JR
Institut für Klinische Chemie und Laboratoriumsmedizin, Zentrallaboratorium, Westfälische Wilhelms-Universität, Albert Schweizer Strasse 33, D-48149 Münster, Germany.
Pulawski
E
E
Junker
R
R
Seedorf
U
U
Assmann
G
G
Zidek
W
W
Tepel
M
M
D015764:Bepridil / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008954:Models, Biological; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*; D019284:Thapsigargin / Q000494:pharmacology*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019831:Sodium-Calcium Exchanger; D019284:Thapsigargin; D015764:Bepridil; C038983:1,3-dimethylthiourea; D012964:Sodium; D000252:Calcium-Transporting ATPases; D013890:Thiourea; D002118:Calcium