Endothelin converting enzyme activity in primary rat astrocytes is modulated by endothelin B receptors

Astrocytes express endothelin-1 (ET-1), ET-3, and their receptors, ETA and ETB. We report here that activated astrocytes in vivo also express endothelin converting enzyme-1 (ECE-1). Higher basal ET-1 concentrations in astrocyte media from ETB-deficient (sl/sl) versus wildtype (+/+) rats suggested th...

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Hauptverfasser: Ehrenreich, Hannelore (VerfasserIn) , Löffler, Bernd-Michael (VerfasserIn) , Hasselblatt, Martin (VerfasserIn) , Langen, Hanno (VerfasserIn) , Oldenburg, Jan (VerfasserIn) , Subkowski, Thomas (VerfasserIn) , Schilling, Lothar (VerfasserIn) , Sirén, Anna-Leena (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 1999
In: Biochemical and biophysical research communications
Year: 1999, Jahrgang: 261, Heft: 1, Pages: 149-155
ISSN:1090-2104
DOI:10.1006/bbrc.1999.0924
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1006/bbrc.1999.0924
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0006291X99909245
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Verfasserangaben:Hannelore Ehrenreich, Bernd-Michael Löffler, Martin Hasselblatt, Hanno Langen, Jan Oldenburg, Thomas Subkowski, Lothar Schilling, and Anna-Leena Sirén
Beschreibung
Zusammenfassung:Astrocytes express endothelin-1 (ET-1), ET-3, and their receptors, ETA and ETB. We report here that activated astrocytes in vivo also express endothelin converting enzyme-1 (ECE-1). Higher basal ET-1 concentrations in astrocyte media from ETB-deficient (sl/sl) versus wildtype (+/+) rats suggested that altered ECE activity may be related to the absence of ETB receptors. Quantification of ECE activity in membranes from sl/sl astrocytes yielded a 50% higher conversion compared to +/+ astrocytes, with indistinguishable ECE-1 mRNA and protein levels. Kinetic analysis of ECE activity revealed similar Vmax values in sl/sl and +/+ astrocytes. Enzyme activity was competitively inhibited by phosphoramidon with Ki values of 0.6 and 0.3 μM, respectively. The Km value of ECE was 0.5 μM in +/+ and 0.2 μM in sl/sl astrocytes. Two-dimensional focussing of astrocytic ECE-1 uncovered heterogeneity of charge and molecular weight. ECE-1 from sl/sl revealed a glycosylation pattern different from +/+ astrocytes. In conclusion, the ETB receptor may, via ECE-1 glycosylation, exert a negative feedback on ECE activity in the astrocytic endothelin system.
Beschreibung:Available online 25 May 2002
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Beschreibung:Online Resource
ISSN:1090-2104
DOI:10.1006/bbrc.1999.0924