Calmodulin antagonist W7 increases inositol phosphates in insulin secreting RINm5F cells

W7, a calmodulin antagonist, has been reported to increase cytosolic free calcium concentration [Ca2+]i in non stimulated rat insulinoma cells (RINm5F). And this effect was not due to enhanced calcium uptake. In the present study the effect of calmodulin antagonist W7 on the inositol phosphate turnover of RINm5F cells was studied. Inositol phosphates were separated using a new modified technique of anion-exchange high performance liquid chromatography (HPLC). It was observed that W7 significantly increased inositol trisphosphate and inositol bisphosphate within 5 and 15 sec, respectively. No changes of inositol phosphates were detected employing W5, a chlorine-deficient analogue of W7 without calmodulin antagonistic action. Our data are in favour of the view that (I) calmodulin may be involved in inositol phosphate metabolism of RINm5F cells and that (II) the increase of [Ca2+]i in response to W7 as reported previously may be due to elevation of inositol trisphosphate.