PMID- 8717356
OWN - NLM
STAT- MEDLINE
DCOM- 19961011
LR  - 20190826
IS  - 0169-328X (Print)
IS  - 0169-328X (Linking)
VI  - 35
IP  - 1-2
DP  - 1996 Jan
TI  - Dopaminergic regulation of striatonigral tachykinin and dynorphin gene 
      expression: a study with the dopamine uptake inhibitor GBR-12909.
PG  - 197-210
AB  - The present study examined the modulatory role of dopamine (DA) on striatonigral 
      preprotachykinin (PPT) and prodynorphin (PD) gene expression, employing the DA 
      uptake inhibitor, GBR-12909 (GBR), as a tool. The striatal and nigral levels of 
      tachykinin (substance P (SP), neurokinin A (NKA)) and dynorphin (dynorphin A(1-8) 
      (DYN)) peptides were determined by radioimmunoassays. The abundance of mRNAs in 
      the striatum was quantified by Northern blot analysis. The rate of transcription 
      of PPT and PD genes in the striatum was measured by transcription run-on assays. 
      A regimen of repeated administration of GBR (20 mg/kg/day, i.p., for 1-4 days) to 
      female Sprague-Dawley rats increased striatal and nigral SP, NKA, and DYN peptide 
      levels. The increased peptide levels were associated with increases in the 
      abundance of PD mRNA and PPT mRNA and increases in the rate of transcription of 
      PD and PPT genes in the striatum, suggesting a GBR-induced activation of the 
      striatonigral tachykinin and dynorphin neurons. Dopaminergic denervation with 
      6-hydroxydopamine (6OHDA) blocked the GBR-induced increases in SP and DYN and PPT 
      and PD mRNAs. The concurrent administration of the D1 DA antagonist, SCH-23390, 
      blocked the GBR-induced increases in SP, NKA and PPT mRNA but failed to affect 
      DYN or PD mRNA levels; the concurrent administration of the D2 DA antagonist, 
      spiperone, blocked the GBR-induced increases in SP, NKA and PPT mRNA and also DYN 
      and PD mRNA. The study reveals that repeated administration of GBR enhances the 
      levels of tachykinin and dynorphin peptides in striatonigral neurons by a 
      stimulus-transcription-biosynthesis coupling mechanism. The GBR-induced effects 
      are dependent on the integrity of nigrostriatal dopaminergic neurons and the 
      presence of D1 and/or D2 DA receptors.
FAU - Sivam, S P
AU  - Sivam SP
AD  - Department of Pharmacology & Toxicology, Indiana University School of Medicine, 
      Gary 46408, USA.
LA  - eng
GR  - NS 26063/NS/NINDS NIH HHS/United States
GR  - S07RR5371/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res Mol Brain Res
JT  - Brain research. Molecular brain research
JID - 8908640
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - 0 (Enkephalins)
RN  - 0 (Piperazines)
RN  - 0 (Protein Precursors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tachykinins)
RN  - 0 (preprotachykinin)
RN  - 74913-18-1 (Dynorphins)
RN  - 90X28IKH43 (vanoxerine)
RN  - 93443-35-7 (preproenkephalin)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Cell Nucleus/metabolism
MH  - Corpus Striatum/drug effects/*metabolism
MH  - Denervation
MH  - Dopamine/*physiology
MH  - Dopamine Uptake Inhibitors/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Dynorphins/biosynthesis
MH  - Enkephalins/*biosynthesis
MH  - Female
MH  - *Gene Expression Regulation/drug effects
MH  - Kinetics
MH  - Organ Specificity
MH  - Piperazines/*pharmacology
MH  - Protein Precursors/*biosynthesis
MH  - RNA, Messenger/analysis/biosynthesis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Substantia Nigra/drug effects/*metabolism
MH  - Tachykinins/*biosynthesis
MH  - Transcription, Genetic/*drug effects
EDAT- 1996/01/01 00:00
MHDA- 1996/01/01 00:01
CRDT- 1996/01/01 00:00
PHST- 1996/01/01 00:00 [pubmed]
PHST- 1996/01/01 00:01 [medline]
PHST- 1996/01/01 00:00 [entrez]
AID - 0169-328X(95)00216-F [pii]
AID - 10.1016/0169-328x(95)00216-f [doi]
PST - ppublish
SO  - Brain Res Mol Brain Res. 1996 Jan;35(1-2):197-210. doi: 
      10.1016/0169-328x(95)00216-f.