Document Detail

Level of ETB receptor mRNA is down-regulated by endothelins through decreasing the intracellular stability of mRNA molecules.
MedLine Citation:
PMID:  1321607     Owner:  NLM     Status:  MEDLINE    
Using ROS17/2 rat osteosarcoma cells as a model system, we examined the possibility that endothelin (ET)-induced down-regulation of ETB receptor was accompanied by a decrease in levels of ETB receptor mRNA. Northern blot analysis showed that low doses of ET-1 and ET-3 caused a transient decrease in ETB receptor mRNA in the cells. The maximum decrease in the levels of ETB receptor mRNA (80%) occurred after 2-4 h of exposure of the cells to ETs and was followed by a gradual recovery to control levels by 24 h. The effects were dose-dependent (EC50-1 nM), and ET-1 and ET-3 were almost equipotent in eliciting the response. The addition of either ionomycin, a Ca2+ ionophore, or phorbol dibutyrate, a protein kinase C activator, mimicked the effect of ETs. These results suggested that ETs-induced down-regulation of ETB receptor mRNA was mediated by the activation of ETB receptor and that it may have involved ETB receptor coupled second messenger pathways. We also showed that ETB receptor mRNA had a long intracellular life span which suggested that ETs-induced down-regulation of ETB receptor mRNA may have been due to a decrease in the stability of mRNA, rather than inactivation of the transcription of mRNA.
T Sakurai; H Morimoto; Y Kasuya; Y Takuwa; H Nakauchi; T Masaki; K Goto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  186     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  1992 Jul 
Date Detail:
Created Date:  1992-08-14     Completed Date:  1992-08-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  342-7     Citation Subset:  IM    
Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan.
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MeSH Terms
Blotting, Northern
Cell Line
Endothelins / metabolism,  pharmacology*
Gene Expression Regulation, Neoplastic / drug effects
Ionomycin / pharmacology
Phorbol 12,13-Dibutyrate / pharmacology
RNA, Messenger / isolation & purification,  metabolism*
RNA, Neoplasm / genetics,  isolation & purification
Receptors, Cell Surface / genetics*
Receptors, Endothelin
Reg. No./Substance:
0/Endothelins; 0/RNA, Messenger; 0/RNA, Neoplasm; 0/Receptors, Cell Surface; 0/Receptors, Endothelin; 37558-16-0/Phorbol 12,13-Dibutyrate; 56092-81-0/Ionomycin

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