Inhibitory action of fatty acids on calcium fluxes in thyroid FRTL-5 cells

In the present study, we wanted to investigate the action of fatty acids on agonist-evoked changes in intracellular free calcium ([Ca 2+] i) in thyroid FRTL-5 cells. Stimulating Fura 2 loaded cells with long chain unsaturated fatty acids increased [Ca 2+] i in a dose-dependent manner. This increase was in part dependent on extracellular calcium. Long chain saturated fatty acids and short chain fatty acids had no effects on [Ca 2+] i per se. Pretreatment of the cells with long chain unsaturated fatty acids almost totally inhibited both the ATP- and thapsigargin-evoked release of sequestered calcium and the entry of extracellular calcium. Long chain saturated fatty acids also attenuated the ATP-evoked increase in [Ca 2+] i, while short chain fatty acids had no effects on the ATP-evoked change in [Ca 2+] i. The inhibitory effect of long chain unsaturated fatty acids on agonist-evoked changes in [Ca 2+] i was not dependent on activation of protein kinase C, and was not due to an enhanced efflux of calcium. These fatty acids rapidly acidified the cytosol in the cells, which could, in part, explain the inhibitory effect of the long chain unsaturated fatty acids on agonist-evoked changes in [Ca 2+] i. Addition of bovine serum albumin to the cells rapidly reversed the inhibitory effect of the fatty acids on [Ca 2+] i, and restored pH i. Thus, fatty acids could be potential modulators of calcium signaling in FRTL-5 cells, possibly by modulating calcium entry at the level of the plasma membrane.