THE IMIDAZOLINE DERIVATIVE CALMIDAZOLIUM INHIBITS VOLTAGE-GATED CA2-CHANNELS AND INSULIN RELEASE BUT HAS NO EFFECT ON THE PHOSPHOLIPASE-C SYSTEM IN INSULIN-PRODUCING RINM5F-CELLS()

The present study shows that the calmodulin antagonist calmidazolium i nhibited influx of Ca2+ through voltage-gated Ca2+-channels in clonal insulin producing RINm5F-cells. The mechanism of inhibition may involv e both Ca2+-calmodulin-dependent protein kinases and direct binding of calmidazolium to the Ca2+-channel. Calmidazolium did not affect uptak e of Ca2+ into intracellular Ca2+-pools, inositol 1,4,5-trisphosphate (InsP(3)) formation or action on intracellular Ca2+-pools. The calmodu lin inhibitor also did not affect glucose utilization or oxidation in RINm5F-cells, speaking against an unspecific toxic effect of the compo und. KCl-and ATP-stimulated insulin release from RINm5F-cells was atte nuated by calmidazolium, whereas basal hormone secretion was unaffecte d.