PMID- 12095161
OWN - NLM
STAT- MEDLINE
DCOM- 20030128
LR  - 20221207
IS  - 1535-1084 (Print)
IS  - 1535-1084 (Linking)
VI  - 1
IP  - 3
DP  - 2002
TI  - 5-HT2A receptor activation leads to increased BDNF mRNA expression in C6 glioma 
      cells.
PG  - 197-205
AB  - It has recently been suggested that an increase in brain-derived neurotrophic 
      factor (BDNF) expression may mediate some of the therapeutic effect of 
      antidepressant drugs, via their effects on the neurotransmitter 
      5-hydroxytryptamine (5-HT). However, because it is unclear whether 5-HT 
      manipulations directly affect BDNF expression, we examined BDNF mRNA levels in C6 
      glioma cells following incubation with 5-HT using reverse transcription 
      polymerase chain reaction (RT-PCR) and Northern blot analysis. Incubation of C6 
      glioma cells with 5-HT increased the BDNF mRNA expression approx twofold. The 
      effect of 5-HT (100 microM) was inhibited by a 5-HT2A receptor antagonist 
      (ketanserin; 1 microM). The RNA synthesis inhibitor (actinomycin D; 10 
      microg/mL), but not a protein synthesis inhibitor (cycloheximide; 0.5 microg/mL) 
      blocked the effect of 5-HT. Furthermore, incubation of C6 glioma cells with EGTA 
      (1 mM), a protein kinase inhibitor (staurosporine; 1 microM), the Ca2+ ATPase 
      inhibitor thapsigargin (1 microM), or a calcium/calmodulin-dependent kinase 
      inhibitor (KN 62; 1 microM) inhibited the response to 5-HT. Our data show that 
      5-HT increases de novo BDNF mRNA synthesis following direct activation of the 
      5-HT2A receptor, via a calcium-dependent and protein kinase-dependent pathway.
FAU - Meller, Robert
AU  - Meller R
AD  - Smithkline Beecham Centre for Applied Neuropsychobiology, University Department 
      of Clinical Pharmacology, Radcliffe Infirmary, Oxford. 
      rmeller@downneurobiology.org
FAU - Babity, Joseph M
AU  - Babity JM
FAU - Grahame-Smith, David G
AU  - Grahame-Smith DG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neuromolecular Med
JT  - Neuromolecular medicine
JID - 101135365
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nucleic Acid Synthesis Inhibitors)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor, Serotonin, 5-HT2A)
RN  - 0 (Receptors, Serotonin)
RN  - 0 (Serotonin Antagonists)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 333DO1RDJY (Serotonin)
RN  - EC 2.7.- (Protein Kinases)
SB  - IM
MH  - Animals
MH  - Brain/*drug effects/metabolism/physiopathology
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Calcium Signaling/drug effects/physiology
MH  - Depressive Disorder/*drug therapy/metabolism/physiopathology
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression/drug effects/physiology
MH  - Neurons/*drug effects/metabolism
MH  - Nucleic Acid Synthesis Inhibitors/pharmacology
MH  - Protein Kinases/drug effects/metabolism
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - RNA, Messenger/drug effects/metabolism
MH  - Rats
MH  - Receptor, Serotonin, 5-HT2A
MH  - Receptors, Serotonin/*drug effects/metabolism
MH  - Serotonin/metabolism/pharmacology
MH  - Serotonin Antagonists/pharmacology
MH  - Selective Serotonin Reuptake Inhibitors/*pharmacology
MH  - Tumor Cells, Cultured
MH  - Up-Regulation/*drug effects/physiology
EDAT- 2002/07/04 10:00
MHDA- 2003/01/29 04:00
CRDT- 2002/07/04 10:00
PHST- 2002/02/07 00:00 [received]
PHST- 2002/02/28 00:00 [accepted]
PHST- 2002/07/04 10:00 [pubmed]
PHST- 2003/01/29 04:00 [medline]
PHST- 2002/07/04 10:00 [entrez]
AID - NMM:1:3:197 [pii]
AID - 10.1385/NMM:1:3:197 [doi]
PST - ppublish
SO  - Neuromolecular Med. 2002;1(3):197-205. doi: 10.1385/NMM:1:3:197.