ACLARUBICIN INHIBITS PHOSPHATIDYLINOSITOL HYDROLYSIS AND CONTRACTION OF RAT AORTA

The effects of aclarubicin on phosphatidylinositol hydrolysis and contractile responses were investigated in isolated rat aorta. In the aclarubicin-pretreated aorta, the basal level of [H-3]inositol monophosphate accumulation was significantly lower whereas [H-3]phosphoinositide formation was significantly higher than in the saline-pretreated control aorta. Phenylephrine-, 5-hydroxytryptamine- and sodium fluoride-stimulated increases in [H-3]inositol monophosphate accumulation were also significantly seduced in the aclarubicin-treated aorta compared to the control. Contractile farces induced by 5-hydroxytryptamine and sodium fluoride were markedly diminished in the aclarubicin-treated aorta. These results suggest that aclarubicin inhibits phosphatidyl-inositol hydrolysis at a level of phospholipase C activation, which is involved in the reduction of agonist-induced contraction of rat aorta.