Document Detail

Endothelin ETB receptor signaling in the median eminence and subfornical organ of the rat brain.
MedLine Citation:
PMID:  15464196     Owner:  NLM     Status:  MEDLINE    
We investigated the effect of endothelins (ETs) on receptor-mediated phosphoinositides (PI) turnover in whole subfornical organ (SFO) and median eminence (ME). Consistent with the presence of a high density of binding sites in the SFO and the ME of the rat brain, our results show an increase in PI hydrolysis induced by ETs in each structure, in a dose-dependent manner and with similar ED50 values. In addition, IRL 1620, a selective ETB receptor agonist, increased the inositol monophosphate (InsP1) accumulation in the SFO and the ME in a similar degree as ETs. With the use of selective agonists and antagonists of both endothelin receptor subtypes, we characterized the receptor subtype involved in ET-induced phosphoinositide metabolism. The addition of two selective ETA receptor antagonists, BQ 123 or BQ 610, did not alter the ETs-induced increase in the PI metabolism. While, IRL 1620- and ET3-induced InsP1 accumulation was completely blocked by BQ 788, a selective ETB receptor antagonist, in both brain structures evaluated. Our results demonstrate that in the SFO and the ME of the rat brain, stimulation of phosphoinositide turnover constitutes one of the signaling pathways of ETs, and this action is mediated through ETB receptor activation. These results support the concept that endothelin could play a role in the regulation of brain functions.
María del Rosario Garrido; Anita Israel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neuropeptides     Volume:  38     ISSN:  0143-4179     ISO Abbreviation:  Neuropeptides     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-10-06     Completed Date:  2005-03-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8103156     Medline TA:  Neuropeptides     Country:  Scotland    
Other Details:
Languages:  eng     Pagination:  304-10     Citation Subset:  IM    
School of Pharmacy, Laboratory of Neuropeptides, Universidad Central de Venezuela, Apartado Postal 50176, Sabana Grande 1050A, Caracas, Venezuela.
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MeSH Terms
Antihypertensive Agents / metabolism,  pharmacology
Binding Sites
Dose-Response Relationship, Drug
Endothelin-1 / metabolism,  pharmacology*
Endothelin-3 / metabolism,  pharmacology*
Median Eminence / drug effects,  metabolism*
Oligopeptides / metabolism,  pharmacology
Peptides, Cyclic / metabolism,  pharmacology
Phosphatidylinositols / metabolism
Rats, Sprague-Dawley
Receptor, Endothelin A / antagonists & inhibitors,  metabolism
Receptor, Endothelin B / antagonists & inhibitors,  metabolism*
Signal Transduction / physiology*
Subfornical Organ / drug effects,  metabolism*
Reg. No./Substance:
0/Antihypertensive Agents; 0/Endothelin-1; 0/Endothelin-3; 0/Oligopeptides; 0/Peptides, Cyclic; 0/Phosphatidylinositols; 0/Receptor, Endothelin A; 0/Receptor, Endothelin B; 136553-81-6/cyclo(Trp-Asp-Pro-Val-Leu); 141595-53-1/BQ 610

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