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Stretch induced endothelin-1 secretion by adult rat astrocytes involves calcium influx via stretch-activated ion channels (SACs).
Ostrow, Lyle W; Suchyna, Thomas M; Sachs, Frederick.
Afiliação
  • Ostrow LW; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA. lostrow1@jhmi.edu
Biochem Biophys Res Commun ; 410(1): 81-6, 2011 Jun 24.
Article em En | MEDLINE | ID: mdl-21640709
ABSTRACT
The expression of endothelins (ETs) and ET-receptors is often upregulated in brain pathology. ET-1, a potent vasoconstrictor, also inhibits the expression of astrocyte glutamate transporters and is mitogenic for astrocytes, glioma cells, neurons, and brain capillary endothelia. We have previously shown that mechanical stress stimulates ET-1 production by adult rat astrocytes. We now show in adult astrocytes that ET-1 production is driven by calcium influx through stretch-activated ion channels (SACs) and the ET-1 production correlates with cell proliferation. Mechanical stimulation using biaxial stretch (<20%) of a rubber substrate increased ET-1 secretion, and 4 µM GsMTx-4 (a specific inhibitor of SACs) inhibited secretion by 30%. GsMTx-4 did not alter basal ET-1 levels in the absence of stretch. Decreasing the calcium influx by lowering extracellular calcium also inhibited stretch-induced ET-1 secretion without effecting ET-1 secretion in unstretched controls. Furthermore, inhibiting SACs with the less specific inhibitor streptomycin also inhibited stretch-induced ET-1 secretion. The data can be explained with a simple model in which ET-1 secretion depends on an internal Ca(2+) threshold. This coupling of mechanical stress to the astrocyte endothelin system through SACs has treatment implications, since all pathology deforms the surrounding parenchyma.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Estresse Mecânico / Astrócitos / Cálcio / Endotelina-1 / Canais Iônicos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Biochem Biophys Res Commun Ano de publicação: 2011 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Estresse Mecânico / Astrócitos / Cálcio / Endotelina-1 / Canais Iônicos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Biochem Biophys Res Commun Ano de publicação: 2011 Tipo de documento: Article País de afiliação: Estados Unidos