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Stimulation of Phosphatidylinositol Hydrolysis by Brain‐Derived Neurotrophic Factor and Neurotrophin‐3 in Rat Cerebral Cortical Neurons Developing in Culture
Author(s) -
Widmer Hans R.,
Knüsel Beat,
Hefti Franz
Publication year - 1992
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.1471-4159.1992.tb10102.x
Subject(s) - neurotrophin , nerve growth factor , neurotrophic factors , phosphatidylinositol , biology , trk receptor , medicine , stimulation , inositol , endocrinology , brain derived neurotrophic factor , microbiology and biotechnology , inositol phosphate , second messenger system , neuroscience , signal transduction , receptor , biochemistry
Phosphatidylinositol (PI) breakdown represents a powerful system participating in the transduction mechanism of some neurotransmitters and growth factors and producing two second messengers, diacylglycerol and inositol trisphosphate. The transformation of PC12 neuroblastoma cells into neuron‐like cells induced by nerve growth factor (NGF) is preceded by a rapid stimulation of PI breakdown; however, it was not known whether PI breakdown mediates actions of other members of the neurotrophin family. The present study analyzed the effects of NGF, brain‐derived neurotrophic factor (BDNF), and neurotrophin‐3 (NT‐3) on PI breakdown in primary cultures of embryonic rat brain cells. Cultures were grown for 7 days; PI was then labeled by incubating cultures with myo ‐[ 3 H]inositol, which then were exposed acutely to growth factors. BDNF and NT‐3, but not NGF, elevated the levels of labeled inositol phosphates within 10–15 min after addition to the cultures in a dose‐dependent manner. ED 50 values for BDNF and NT‐3 were 12.4 and 64.5 ng/ml, respectively. Comparable effects were found in cultures of cortical, striatal, and septal cells. The actions of BDNF and NT‐3 probably reflect actions on neurons, because no effects were seen in cultures of nonneuronal cells. In contrast, basic fibroblast growth factor induced a marked stimulation of PI breakdown in cultures of nonneuronal cells. K252b, which selectively blocks neurotrophin actions by inhibiting trk ‐type receptor proteins, prevented the PI breakdown mediated by BDNF and NT‐3. The findings suggest that rapid and specific induction of PI breakdown is involved in the signal transduction of BDNF and NT‐3, and they provide evidence that cortical neurons are functionally responsive to BDNF and NT‐3 during development.