[Phenylarsine oxide, a tyrosine phosphatase inhibitor, induces an increase in the intracellular concentration of calcium in rat peritoneal macrophages and human fibroblasts].
Using Fura-2 microfluorimetry, phenylarsine oxide (PAO) (10-50 microM), a potent tyrosine phosphatase inhibitor, was shown to induce a dose-dependent increase in the free Ca2+ intracellular concentration in rat peritoneal macrophages and human foreskin fibroblasts. The PAO-induced increase in [Ca2+]i is not due presumably to depletion of intracellular Ca2+ stores but to mainly a stimulation of Ca2+ entry from the extracellular medium. This PAO-activated Ca2+ entry is attenuated by the following pharmacological agents. Organic and inorganic Ca2+ channel blockers: (nifedipine, verapamil and Ni2+); nonselective cation channel blocker niflumic acid; tyrosine kinase inhibitors genistein and methyl-2,5-dihydroxycinnamate; SH-reagents dithiothreitol parachloromercuribenzoate and N-ethylmaleimide; arachidonic acid metabolism inhibitors 4-bromophenacyl bromide, indomethacin and caffeic acid; microtubule disrupters vinblastine, colchicine and colcemide. On the contrary, microfilament disrupters, cytochalasin B and phalloidin, enhance PAO-activated Ca2+ entry. Our data suggest that the dynamic balance between tyrosine kinase and phosphatase activity may play a central role in the maintenance of homeostatic levels of [Ca2+]i both in unstimulated cells and after agonist application.
Krutetskaia
Z I
ZI
Physiological Research Institute, St. Petersburg State University.
Lebedev
O E
OE
Krutetskaia
N I
NI
Butov
S N
SN
Petrova
T V
TV
D000818:Animals; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism; D001152:Arsenicals / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002460:Cell Line; D003599:Cytoskeleton / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013439:Sulfhydryl Reagents / Q000494:pharmacology
D001152:Arsenicals; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D013439:Sulfhydryl Reagents; C029341:oxophenylarsine; D016718:Arachidonic Acid; D017027:Protein Tyrosine Phosphatases; D002118:Calcium
Ingibitor tirozinfosfataz fenilarzinoksid indutsiruet uvelichenie vnutrikletochnoĭ kontsentratsii Ca2+ v peritoneal'nykh makrofagakh krysy i fibroblastakh cheloveka.