In the present study, we investigated the role of the extracellular signal-regulated protein kinase (ERK) in regulation of the hypoxia marker, carbonic anhydrase IX (CAIX). U0126, a specific inhibitor of MEK1/2, downregulated CAIX expression induced by true hypoxia and cell density. CA9 promoter act
Role of the astrocytic ETB receptor in the regulation of extracellular endothelin-1 during hypoxia
✍ Scribed by Martin Hasselblatt; Piotr Lewczuk; Bernd-Michael Löffler; Heike Kamrowski-Kruck; Nicolas Von Ahsen; Anna-Leena Sirén; Hannelore Ehrenreich
- Publisher
- John Wiley and Sons
- Year
- 2001
- Tongue
- English
- Weight
- 267 KB
- Volume
- 34
- Category
- Article
- ISSN
- 0894-1491
No coin nor oath required. For personal study only.
✦ Synopsis
Astrocytes are known to possess an effective endothelin (ET) eliminatory system which involves astrocytic ET A and ET B receptors and may become particularly relevant under pathophysiological conditions. The present study has therefore been designed to explore the effect of standardized hypoxia on extracellular concentrations of endothelin-1 (ET-1) and on endothelin-converting enzyme (ECE) activity in primary rat astrocytes genetically (sl/sl) or experimentally (dexamethasone) deficient in ET B receptors. The results revealed (1) a hypoxia-mediated decrease of extracellular ET-1 in wildtype astrocytes (ϩ/ϩ) that was not observed in ET B -deficient (sl/sl) cultures;
(2) an ET receptor antagonist-induced increase in ET-1 in the media of both genotypes with further elevation upon hypoxia in ϩ/ϩ cultures only; (3) augmentation of the dexamethasone-induced increase in extracellular ET-1 by hypoxia in ϩ/ϩ, but not in sl/sl cultures; (4) synergistic reduction of ET B gene transcription by hypoxia and dexamethasone; and (5) significant increases in endothelin-converting enzyme activity in the presence of hypoxia. To conclude, hypoxia stimulates astrocytic release of mature ET-1. This stimulation is (over)compensated for by increased ET-1 binding to functional ET B receptors. ET B deficiency, whether genetic or experimentally induced, impairs elimination of extracellular ET-1.
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