Effects of arachidonyltrifluoromethyl ketone on cytosolic [Ca2+] in HIT insulinoma cells

Abstract

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 ATFMK. These results suggest a disruptive effect of ATFMK on calcium mobilization which may contribute to its effects on insulin secretion from β-cells.