PMID- 9160348
OWN - NLM
STAT- MEDLINE
DCOM- 19970724
LR  - 20190831
IS  - 0015-5691 (Print)
IS  - 0015-5691 (Linking)
VI  - 109
IP  - 4
DP  - 1997 Apr
TI  - [Specific regulation of gene expression in brain by antisense 
      oligodeoxynucleotides].
PG  - 187-91
AB  - The synthetic oligodeoxynucleotide (ODN) complementary to the normal (sense) 
      mRNA, so-called antisense ODN, has been used to regulate the gene expression in 
      the brain. It has been reported to interfere with transcription, pre-mRNA 
      splicing and translation through at least two mechanisms; i.e., its competition 
      with transcription and protein synthesis machinery or induction of mRNA cleavage. 
      The unmodified antisense ODN was shown to be the RNase activator when it 
      hybridizes with at least four contiguous bases of mRNA. In contrast, the 
      phosphorothioate ODN (S-ODN) is reported to be a less effective activator of RNas 
      II and more resistant to the nuclease attack than unmodified ODN. Because of 
      these properties, S-ODNs are preferentially employed in antisense ODN 
      experiments. When the DNA sequence of the target gene is determined, we can 
      design an antisense ODN that selectively hybridizes with the bases of a nucleic 
      acid (DNA or RNA) related to the target gene. The initial sites of specific 
      binding of most drugs are known to be proteins such as receptors and enzymes. 
      Therefore, the specific modulation of target protein synthesis by the antisense 
      ODN method is quite interesting to the pharmacologist. We have studied the change 
      in the morphine-induced behaviors after the microinjection of antisense S-ODN 
      directed against the m-opioid receptor (MOR) into the periaqueductal gray (PAG) 
      or lateral ventricle of rat brain. We could detect the decrease of the MOR mRNA 
      level in PAG by the RT-PCR method and that in whole brain by the Northern blot 
      technique. Although the antisense ODN method seems to be quite useful for the 
      modulation of a given gene expression, many problems still remain to be 
      elucidated. These include the mechanism of the regulation of a target gene, 
      pharmacokinetics of antisense ODN and toxicity of antisense ODN.
FAU - Yoshikawa, M
AU  - Yoshikawa M
AD  - Department of Pharmacology, Tokai University School of Medicine, Isehara, Japan.
FAU - Oka, T
AU  - Oka T
LA  - jpn
PT  - English Abstract
PT  - Journal Article
PT  - Review
PL  - Japan
TA  - Nihon Yakurigaku Zasshi
JT  - Nihon yakurigaku zasshi. Folia pharmacologica Japonica
JID - 0420550
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Opioid, mu)
SB  - IM
MH  - Animals
MH  - Brain/*metabolism
MH  - *Gene Expression Regulation
MH  - Male
MH  - *Oligonucleotides, Antisense
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/analysis/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Opioid, mu/genetics/*metabolism
RF  - 10
EDAT- 1997/04/01 00:00
MHDA- 1997/04/01 00:01
CRDT- 1997/04/01 00:00
PHST- 1997/04/01 00:00 [pubmed]
PHST- 1997/04/01 00:01 [medline]
PHST- 1997/04/01 00:00 [entrez]
AID - 10.1254/fpj.109.187 [doi]
PST - ppublish
SO  - Nihon Yakurigaku Zasshi. 1997 Apr;109(4):187-91. doi: 10.1254/fpj.109.187.