The membranes of cultured rat brain astrocytes contain endothelin-converting enzyme activity.
Both endothelins and their big-endothelin precursors were found capable of inducing the release of arachidonic acid from purified cultures of rat astrocytes. Their order of potency was as follows: big-endothelin-3 < big-endothelin-1 < endothelin-1 = endothelin-3. Mature endothelins induced the release of arachidonic acid in a rapid fashion. In contrast, much longer incubation times were required for big-endothelins to exert an effect, suggesting that their activity was dependent on their conversion. When big-endothelin-1 was added to the incubation medium of intact live astrocytes, it was converted into mature endothelin-1 in a time-dependent manner and the conversion was inhibited by phosphoramidon. This suggests that astrocytic endothelin-converting enzyme is (at least in part) an external membrane-bound metalloprotease. Some conversion of big-endothelin-3 into endothelin-3 also occurred. However, it was less efficient than the conversion of big-endothelin-1, which is compatible with the lower bioactivity of big-endothelin-3 vs. that of big-endothelin-1 in astrocytes.
Deschepper
C F
CF
MRC Multidisciplinary Research Group on Hypertension, Institut de Recherches Cliniques de Montréal (IRCM), Québec, Canada.
Houweling
A D
AD
Picard
S
S
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D001253:Astrocytes / Q000166:cytology / Q000201:enzymology*; D001667:Binding, Competitive; D002478:Cells, Cultured; D004027:Diencephalon / Q000166:cytology / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D019332:Endothelin-1; D019334:Endothelin-3; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000494:pharmacology*; D005625:Frontal Lobe / Q000166:cytology / Q000201:enzymology; D006020:Glycopeptides / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats
D019332:Endothelin-1; D019334:Endothelin-3; D016232:Endothelins; D006020:Glycopeptides; D011480:Protease Inhibitors; D011498:Protein Precursors; D016718:Arachidonic Acid; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; C008890:phosphoramidon