ET-1 induces cortical spreading depression via activation of the ETA receptor/phospholipase C pathway in vivo.

Details

Serval ID
serval:BIB_D9EC3AF1B805
Type
Article: article from journal or magazin.
Collection
Publications
Title
ET-1 induces cortical spreading depression via activation of the ETA receptor/phospholipase C pathway in vivo.
Journal
American Journal of Physiology. Heart and Circulatory Physiology
Author(s)
Kleeberg J., Petzold G.C., Major S., Dirnagl U., Dreier J.P.
ISSN
0363-6135 (Print)
ISSN-L
0363-6135
Publication state
Published
Issued date
04/2004
Peer-reviewed
Oui
Volume
286
Number
4
Pages
H1339-H1346
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Abstract
Recently, it has been shown that brain topical superfusion of endothelin (ET)-1 at concentrations around 100 nM induces repetitive cortical spreading depressions (CSDs) in vivo. It has remained unclear whether this effect of ET-1 is related to a primary neuronal/astroglial effect, such as an increase in neuronal excitability or induction of interastroglial calcium waves, or a penumbra-like condition after vasoconstriction. In vitro, ET-1 regulates interastroglial communication via combined activation of ET(A) and ET(B) receptors, whereas it induces vasoconstriction via single activation of ET(A) receptors. We have determined the ET receptor profile and intracellular signaling pathway of ET-1-induced CSDs in vivo. In contrast to the ET(B) receptor antagonist BQ-788 and concentration dependently, the ET(A) receptor antagonist BQ-123 completely blocked the occurrence of ET-1-induced CSDs. The ET(B) receptor antagonist did not increase the efficacy of the ET(A) receptor antagonist. Direct stimulation of ET(B) receptors with the selective ET(B) agonist BQ-3020 did not trigger CSDs. The phospholipase C (PLC) antagonist U-73122 inhibited CSD occurrence in contrast to the protein kinase C inhibitor Gö-6983. Our findings indicate that ET-1 induces CSDs through ET(A) receptor and PLC activation. We conclude that the induction of interastroglial calcium waves is unlikely the primary cause of ET-1-induced CSDs. On the basis of the receptor profile, likely primary targets of ET-1 mediating CSD are either neurons or vascular smooth muscle cells.
Keywords
Animals, Arachidonic Acid/pharmacology, Astrocytes/drug effects, Cell Communication/drug effects, Cortical Spreading Depression/drug effects, Endothelin-1/pharmacology, Endothelins/pharmacology, Estrenes/pharmacology, Male, Muscle, Smooth, Vascular/drug effects, Oligopeptides/pharmacology, Parietal Lobe/drug effects, Peptide Fragments/pharmacology, Peptides, Cyclic/pharmacology, Phosphodiesterase Inhibitors/pharmacology, Piperidines/pharmacology, Pyrrolidinones/pharmacology, Rats, Rats, Wistar, Receptor, Endothelin A/antagonists & inhibitors, Receptor, Endothelin A/drug effects, Signal Transduction/drug effects, Type C Phospholipases/physiology
Pubmed
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03/10/2012 22:31
Last modification date
20/08/2019 15:59
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