epidermal-growth-factor and inositol-1-3-4-trisphosphate

In PC12 cells, preincubated with [3H]inositol, nerve growth factor (NGF) stimulated an approximately 100% increase in the levels of [3H]inositol 1,3,4-trisphosphate ([3H]-Ins(1,3,4)P3], [3H]inositol 1,4,5-trisphosphate ([3H]Ins(1,4,5)P3], and [3H]inositol 1,3,4,5-tetrakisphosphate ([3H]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 [3H]Ins(1,3,4)P3, [3H]Ins(1,4,5)P3, and [3H]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 [3H]Ins(1,3,4)P3, [3H]Ins(1,4,5)P3, and [3H]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)P4 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)P4 may be a common response to factors stimulating neuronal differentiation, it is not sufficient for stimulation of neuronal differentiation.

Topics: Animals; Epidermal Growth Factor; Fibroblast Growth Factors; Inositol 1,4,5-Trisphosphate; Inositol Phosphates; Nerve Growth Factors; PC12 Cells

Lithium ion, which inhibits hydrolytic degradation of inositol monophosphates, is the most common therapeutic agent used in the control of bipolar disorder. There exists evidence that elevated elemental vanadium levels may play an etiological role in at least some forms of manic-depression. Here we demonstrate that vanadate treatment of intact cells from several different clonal lines synergistically induces substantial augmentation in neurotransmitter receptor-mediated or growth factor receptor-triggered inositol trisphosphate accumulation in situ. Furthermore, studies done using cellular extracts indicate that effects of vanadate treatment in situ may be due to its ability to inhibit hydrolysis of inositol 1,4,5-trisphosphate inositol 1,3,4-trisphosphate, and inositol 1,3,4,5-tetrakisphosphate in vitro. These results suggest that vanadate treatment may facilitate characterization of inositol phosphate metabolism and intracellular signaling.

Topics: Animals; Carbachol; Cell Line; Clone Cells; Epidermal Growth Factor; Humans; Inositol 1,4,5-Trisphosphate; Inositol Phosphates; Inositol Polyphosphate 5-Phosphatases; Models, Biological; Nerve Growth Factors; Neuroblastoma; PC12 Cells; Phosphatidylinositols; Phosphoric Monoester Hydrolases; Receptors, Neurotransmitter; Vanadates