PMID- 12963488
OWN - NLM
STAT- MEDLINE
DCOM- 20031016
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 66
IP  - 6
DP  - 2003 Sep 15
TI  - Possible involvement of induction of brain-derived neurotrophic factor in the 
      neuroprotective effect of a 5-phenylpyrimidine derivative.
PG  - 1019-23
AB  - When primary cortical neurons prepared from the brains of rat embryos (E18) were 
      cultured in the absence of serum, most of the neurons died after 3 days in vitro. 
      We used this model to discover compounds which support neuronal survival, and 
      found that a new 5-phenylpyrimidine derivative named FU248 
      (2-amino-5-(2,4-dichlorophenyl) pyrimidine) inhibited the neuronal cell death in 
      a dose-dependent manner up to 1 microg/mL. Semiquantitative RT-PCR analysis 
      revealed that an exposure of the primary cortical neurons to 1 microg/mL of FU248 
      transiently and significantly enhanced the expression of genes including 
      brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and 
      neurotrophin-3 (NT-3). The enhancement of the gene expression was maximal 6 hr 
      after the addition of FU248, and the expression returned to the basal level after 
      24 hr. Expression of neurotrophin-4 was not detectable throughout the 
      experimental period. The amount of the transcript for BDNF was approximately nine 
      times and sixteen times more abundant than those for NT-3 and NGF, respectively 
      (t=6 hr). Moreover, an anti-BDNF antibody suppressed the effect of FU248, whereas 
      the control antibody did not show any effects on the neuronal survival. These 
      findings strongly suggest that FU248 exerts its neuroprotective effect, at least 
      in part, through induction of BDNF.
FAU - Matsumoto, Kayo
AU  - Matsumoto K
AD  - Molecular Biology Lab., Medicinal Research Laboratories, Taisho Pharmaceutical 
      Co., Ltd., Yoshino-cho 1-403, Kita-ku, Saitama-shi, Saitama 331-9530, Japan.
FAU - Yamamoto, Kyoko
AU  - Yamamoto K
FAU - Karasawa, Yasuko
AU  - Karasawa Y
FAU - Hino, Noriko
AU  - Hino N
FAU - Nakamura, Atsushi
AU  - Nakamura A
FAU - Takahashi, Masayoshi
AU  - Takahashi M
FAU - Araki, Hiroaki
AU  - Araki H
FAU - Okuyama, Shigeru
AU  - Okuyama S
FAU - Choshi, Tominari
AU  - Choshi T
FAU - Sugino, Eiichi
AU  - Sugino E
FAU - Hibino, Satoshi
AU  - Hibino S
FAU - Yoshimoto, Makoto
AU  - Yoshimoto M
LA  - eng
PT  - Journal Article
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (2-amino-5-(2,4-dichlorophenyl) pyrimidine)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Neurotrophin 3)
RN  - 0 (Pyrimidines)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - P658DCA9XD (neurotrophin 4)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Cell Survival/drug effects
MH  - Cerebral Cortex/cytology
MH  - Gene Expression Profiling
MH  - Nerve Growth Factor/genetics/metabolism
MH  - Nerve Growth Factors/genetics/metabolism
MH  - Neurons/cytology/*drug effects
MH  - Neuroprotective Agents/*pharmacology
MH  - Neurotrophin 3/genetics/metabolism
MH  - Pyrimidines/*pharmacology
MH  - Rats
EDAT- 2003/09/10 05:00
MHDA- 2003/10/17 05:00
CRDT- 2003/09/10 05:00
PHST- 2003/09/10 05:00 [pubmed]
PHST- 2003/10/17 05:00 [medline]
PHST- 2003/09/10 05:00 [entrez]
AID - S0006295203004623 [pii]
AID - 10.1016/s0006-2952(03)00462-3 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2003 Sep 15;66(6):1019-23. doi: 10.1016/s0006-2952(03)00462-3.