PMID- 8348325
OWN - NLM
STAT- MEDLINE
DCOM- 19930914
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 614
IP  - 1-2
DP  - 1993 Jun 18
TI  - Down-regulation of phosphatidylinositol response to BDNF and NT-3 in cultures of 
      cortical neurons.
PG  - 325-34
AB  - The hydrolysis of phosphatidyl 4,5-bisphosphate (PI), which is involved in the 
      transduction mechanism of neurotransmitters and growth factors, is stimulated by 
      brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in primary 
      cultures of fetal brain neurons. In the present study we sought to examine the 
      effect of pretreatment with these factors on their acute stimulation capabilities 
      and, furthermore, to substantiate that the effects of BDNF and NT-3 reflect 
      actions on neurons rather than glial cells. Pretreatment with BNDF and NT-3 for 4 
      days followed by 1 day without growth factor abolished the effect of an acute 
      stimulation with these factors. The growth factors were mutually effective so 
      that BDNF pretreatment abolished the acute response to NT-3 and vice versa. In 
      contrast, the effects of bFGF (basic fibroblast growth factor, a non-neurotrophin 
      growth factor) also stimulating PI hydrolysis in these culture systems, were not 
      reduced by neurotrophin pretreatment. Pretreatment with K-252b, at concentrations 
      known to inhibit trk receptors, did not alter the acute stimulation of PI 
      hydrolysis induced by the neutrophins. PI hydrolysis stimulated by BDNF and NT-3 
      in cultures grown in presence of cytosine arabinoside C, containing > 95% 
      neurons, was higher than in cultures containing non-neuronal cells, indicating 
      that the neurotrophin stimulation occurs in neuronal cells. No stimulatory effect 
      was detected in bFGF treated pure neuronal cultures. The findings suggest that 
      prolonged exposure of responsive neurons to BDNF and NT-3 down-regulates their 
      stimulatory effects on PI hydrolysis.
FAU - Widmer, H R
AU  - Widmer HR
AD  - Division of Neurogerontology, Andrus Gerontology Center, University of Southern 
      California, Los Angeles 90089.
FAU - Ohsawa, F
AU  - Ohsawa F
FAU - Knusel, B
AU  - Knusel B
FAU - Hefti, F
AU  - Hefti F
LA  - eng
GR  - AG09793/AG/NIA NIH HHS/United States
GR  - NS22933/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Carbazoles)
RN  - 0 (Indole Alkaloids)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neurotrophin 3)
RN  - 0 (Phosphatidylinositols)
RN  - 0 (Tetrazolium Salts)
RN  - 0 (Thiazoles)
RN  - 04079A1RDZ (Cytarabine)
RN  - 97161-97-2 (staurosporine aglycone)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EUY85H477I (thiazolyl blue)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Carbazoles/pharmacology
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology/drug effects
MH  - Cytarabine/pharmacology
MH  - Down-Regulation/*drug effects
MH  - Female
MH  - Humans
MH  - Hydrolysis
MH  - Immunohistochemistry
MH  - Indole Alkaloids
MH  - Nerve Growth Factors/antagonists & inhibitors/*pharmacology
MH  - Nerve Tissue Proteins/antagonists & inhibitors/metabolism/*pharmacology
MH  - Neuroglia/drug effects/metabolism
MH  - Neurons/drug effects/metabolism
MH  - Neurotrophin 3
MH  - Phosphatidylinositols/*biosynthesis
MH  - Pregnancy
MH  - Protein Kinase C/antagonists & inhibitors
MH  - Rats
MH  - Tetrazolium Salts
MH  - Thiazoles
EDAT- 1993/06/18 00:00
MHDA- 1993/06/18 00:01
CRDT- 1993/06/18 00:00
PHST- 1993/06/18 00:00 [pubmed]
PHST- 1993/06/18 00:01 [medline]
PHST- 1993/06/18 00:00 [entrez]
AID - 0006-8993(93)91051-S [pii]
AID - 10.1016/0006-8993(93)91051-s [doi]
PST - ppublish
SO  - Brain Res. 1993 Jun 18;614(1-2):325-34. doi: 10.1016/0006-8993(93)91051-s.