CALMODULIN ANTAGONIST W7 INCREASES INOSITOL PHOSPHATES IN INSULIN-SECRETING RINM5F CELLS

W7, a calmodulin antagonist, has been reported to increase cytosolic f ree calcium concentration [Ca2+](i) in non stimulated rat insulinoma c ells (RINm5F). And this effect was not due to enhanced calcium uptake. In the present study the effect of calmodulin antagonist W7 on the in ositol phosphate turnover of RINm5F cells was studied. Inositol phosph ates were separated using a new modified technique of anion-exchange h igh performance liquid chromatography (HPLC). It was observed that W7 significantly increased inositol trisphosphate and inositol bisphospha te within 5 and 15 sec, respectively. No changes of inositol phosphate s were detected employing W5, a chlorine-deficient analogue of W7 with out 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 trispho sphate.