Arachidonyltrifluoromethyl ketone (ATFMK), an analogue of arachidonic acid (AA), inhibits an 85 kDa cytosolic phospholipase A2 enzyme. Exposure of HIT insulinoma cells to ATFMK induced a delayed, sustained, and irreversible increase in cytosolic [Ca2+] that required extracellular Ca2+ and a concentration-dependent inhibition of depolarization-induced increases in cytosolic [Ca2+] prior to onset of the delayed response to AFTMK. These results suggest a disruptive effect of ATFMK on calcium mobilization which may contribute to its effects on insulin secretion from β-cells.
