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Nerve Growth Factor Stimulates the Production of Inositol 1,3,4‐and 1,4,5‐Trisphosphate and Inositol 1,3,4,5‐Tetrakisphosphate in PC 12 Cells
Author(s) -
Contreras M. L.
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb03617.x
Subject(s) - inositol , inositol phosphate , endocrinology , medicine , epidermal growth factor , inositol trisphosphate , nerve growth factor , tyrosine kinase , growth factor , second messenger system , biology , chemistry , receptor
In PC12 cells, preincubated with [ 3 H]inositol, nerve growth factor (NGF) stimulated an ∼ 100% increase in the levels of [ 3 H]inositol 1,3,4‐trisphosphate {[ 3 H]‐Ins(1,3,4)P 3 }, [ 3 H]inositol 1,4,5‐trisphosphate {[ 3 H]lns(1,4,5)P 3 }, and [ 3 H]inositol 1,3,4,5‐tetrakisphosphate {[ 3 H]‐Ins(1,3,4,5)P 4 } 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 [ 3 H]‐Ins(1,3,4)P 3 , [ 3 H]‐Ins(1,4,5)P 3 , and [ 3 H]‐Ins(1,3,4,5)P 4 levels. Using cells cultured in the absence of FBS, epidermal growth factor (EGF) and fibroblast growth factor also stimulated production of [ 3 H]lns(1,3,4)P 3 , [ 3 H]‐Ins(1,4,5)P 3 , and [ 3 H]lns(1,3,4,5)P 4 . 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 lns(1,3,4)P 3 , lns(1,4,5)P 3 , and lns(1,3,4,5)P 4 and that this response is dependent on tyrosine kinase activity. Furthermore, although the production of lns(1,3,4)P 3 , lns(1,4,5)P 3 , and lns(1,3,4,5)P 4 may be a common response to factors stimulating neuronal differentiation, it is not sufficient for stimulation of neuronal differentiation.