EFFECTS OF ARACHIDONYLTRIFLUOROMETHYL KETONE ON CYTOSOLIC [CA2+] IN HIT INSULINOMA CELLS

Arachidonyltrifluoromethyl ketone (ATFMK), an analogue of arachidonic acid (AA), inhibits an 85 kDa cytosolic phospholipase A(2) enzyme. Exp osure of HIT insulinoma cells to ATFMK induced a delayed, sustained, a nd irreversible increase in cytosolic [Ca2+] that required extracellul ar Ca2+ and a concentration-dependent inhibition of depolarization-ind uced increases in cytosolic [Ca2+] prior to onset of the delayed respo nse to AFTMK. These results suggest a disruptive effect of ATFMK on ca lcium mobilization which may contribute to its effects on insulin secr etion from beta-cells. (C) 1997 Elsevier Science B.V.