EFFECTS OF 5,8,11,14-EICOSATETRAYNOIC ACID ON THAPSIGARGIN-INDUCED CALCIUM-ENTRY, AND INTRACELLULAR PH IN THYROID FRTL-5 CELLS

The effect of 5,8,11,14-eicosatetraynoic acid (ETYA), an inhibitor of lipoxygenase and cytochrome P-450 epoxygenase enzymes, on calcium fluxes was investigated in Fura 2 loaded rat thyroid FRTL-5 cells. ETYA per se released sequestered calcium. ETYA also inhibited calcium influx in thapsigargin-stimulated cells in a dose-dependent manner. Addition of calcium to cells treated with ETYA and stimulated with thapsigargin in a calcium-free buffer resulted in a blunted increase in intracellular free calcium compared with the response in control cells. In addition, ETYA per se acidified the cytosol in a dose-dependent manner. Acidification of the cytosol with the K+/H+ ionophore nigericin also decreased thapsigargin-induced calcium entry, but not to the same extent as that seen in cells treated with ETYA. The results suggest that ETYA is a patent modulator of calcium entry, and that part of the inhibitory effect of ETYA may be due to the ETYA-induced acidification of the cytosol.