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 flux es was investigated in Fura 2 loaded rat thyroid FRTL-5 cells. ETYA pe r 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 intracellu lar free calcium compared with the response in control cells. In addit ion, ETYA per se acidified the cytosol in a dose-dependent manner. Aci dification of the cytosol with the K+/H+ ionophore nigericin also decr eased thapsigargin-induced calcium entry, but not to the same extent a s that seen in cells treated with ETYA. The results suggest that ETYA is a patent modulator of calcium entry, and that part of the inhibitor y effect of ETYA may be due to the ETYA-induced acidification of the c ytosol.