The effects of lithium on the phosphoinositides and inositol phosphates of Neurospora crassa

As lithium increased in the growth medium (0–47.4 m M), dry weight, cell wall mass, chitin synthase activity, [ 3H]leucine and [ 3H]adenine incorporation decreased. The levels of the phosphoinositides decreased over 80% while inositol, glycerophosphoinositol (GPI), and the inositol phosphates increased or decreased only slightly. To determine if changes in the phosphoinositides, GPI, and the inositol phosphates occurred soon after exposure to lithium, high concentrations of lithium (47.4 m M) were added to 24-h cultures. At various times after the addition of lithium, mycelial samples were removed and analyzed for changes in the above compounds. In response to lithium, inositol monophosphate accumulated 3.2-fold in 3 h. The activities of enzymes associated with the synthesis of the phosphoinositides and inositol phosphates next were assayed. Inositol 1-phosphate and inositol-4-phosphate phosphatases were the most sensitive to inhibition by lithium. When the enzymes were assayed, their activities were inhibited 92 and 94%, respectively, by lithium chloride (3 m M). Inositol-1,4-phosphate phosphatase and Ca 2+-dependent phosphoinositidase also were inhibited 68 and 32%, respectively, by lithium. The possibility that a phosphatidylinositol cycle exists in Neurospora is discussed.