Activation of calcium entry by cyclopiazonic acid in thyroid FRTL-5 cells.
The aim of the present study was to investigate whether the Ca(2+)-ATPase inhibitor cyclopiazonic acid (CPA) could empty intracellular Ca2+ stores and activate Ca2+ influx in thyroid FRTL-5 cells. Addition of CPA to Fura-2 loaded cells rapidly increased intracellular free Ca2+ ([Ca2+]i) which then stabilized at a new elevated steady state level. The initial increase was mainly dependent on the release of sequestered Ca2+, but was decreased in Ca(2+)-free buffer and in depolarized cells. The plateau phase was totally dependent on extracellular Ca2+. Addition of Ca2+ to cells exposed to CPA in Ca(2+)-free buffer rapidly increased [Ca2+]i. This influx was decreased in depolarized cells and inhibited by SKF 96365. Addition of CPA to cells prior to stimulating the cells with ATP totally abolished the ATP-induced increase in [Ca2+]i. In Ca(2+)-free buffer, addition of ATP prior to CPA decreased the response in [Ca2+]i evoked by CPA. The results show that emptying intracellular Ca2+ stores with CPA rapidly activates influx of Ca2+ in FRTL-5 cells. Furthermore, ATP and CPA appear to release Ca2+, at least in part, from the same intracellular Ca2+ store in these cells.
Endocrine Research Laboratory, University of Helsinki, Minerva Foundation Institute for Medical Research, Finland.
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Törnquist
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002451:Cell Compartmentation / Q000187:drug effects; D002460:Cell Line; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism
D007093:Imidazoles; D007211:Indoles; D007295:Inositol Phosphates; D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium; C000543:cyclopiazonic acid