NERVE GROWTH-FACTOR STIMULATES THE PRODUCTION OF INOSITOL 1,3,4-TRISPHOSPHATE AND 1,4,5-TRISPHOSPHATE AND INOSITOL 1,3,4,5-TETRAKISPHOSPHATE IN PC12 CELLS

In PC12 cells, preincubated with [H-3]inositol, nerve growth factor (NGF) stimulated an approximately 1 00% increase in the levels of [H-3]inositol 1,3,4-trisphosphate {[H-3]-Ins(1,3,4)P3}, [H-3]inositol 1,4,5-trisphosphate [H-3]Ins(1, 4,5)P3 }, and [H-3]inositol 1,3,4,5-tetrakisphosphate {[H-3]Ins(1,3,4,5)P4} as early as 5-15 s after addition of NGF. This NGF-mediated response was apparent only when the cells had been cultured in the absence of fetal bovine serum (FBS). PC12 cells cultured in FBS-containing medium did not display NGF-mediated increases in [H-3]Ins(1,3,4)P3, [H-3]Ins(1,4,5)P3, and [H-3]Ins(1,3,4,5)P4 levels. Using cells cultured in the absence of FBS, epidermal growth factor(EGF) and fibroblast growth factor also stimulated production of [H-3]Ins(1,3,4)P3, [H-3]Ins(1,4,5)P3, and [H-3]Ins(1,3,4,5)P4. Lavendustin A, a tyrosine kinase inhibitor, inhibited both the EGF- and NGF-stimulated increases in the levels of these tritiated inositol phosphates. These results suggest that NGF stimulates the production of Ins(1,3,4)P3, Ins(1,4,5)P3, and Ins(1,3,4,5)P, and that this response is dependent on tyrosine kinase activity. Furthermore, although the production of Ins(1,3,4)P3, Ins(1,4,5)P3, and Ins(1,3,4,5)P, may be a common response to factors stimulating neuronal differentiation, it is not sufficient for stimulation of neuronal differentiation.