Endothelins stimulate the production of stromelysin-1 in cultured rat astrocytes.
The effects of endothelins (ETs) on the production of stromelysins, a sub-family of matrix metalloproteinases, were examined in cultured astrocytes. The treatment of cultured rat astrocytes with ET-1 increased stromelysin-1 mRNA levels, while stromelysin-2 and -3 mRNAs were not affected. Immunocytochemical observations showed that cultured astrocytes produced stromelysin-1 protein. ET-1 and Ala(1,3,11,15)-ET-1, an ET(B) receptor selective agonist, stimulated the release of stromelysin-1 from cultured astrocytes. Accompanying the increase in protein release, the peptidase activity of stromelysin-1 in the medium was also increased by ET-1. The effects of ET-1 on astrocytic stromelysin-1 expression were inhibited by PD98059, staurosporine, and Ca(2+) chelation, but not by SB203580 or pyrrolidine dithiocarbamate. These results show that activation of astrocytic ET receptors stimulates the production of stromelysin-1, suggesting a role for ETs in stromelysin production in brain pathologies.
Koyama
Yutaka
Y
Laboratory of Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, Nishikiori-Kita 3-11-1, Tonda-bayashi, Osaka 584-8540, Japan. koyamay@osaka-ohtani.ac.jp
Tanaka
Kazuhiro
K
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology*; D002478:Cells, Cultured; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology / Q000502:physiology; D016232:Endothelins / Q000494:pharmacology / Q000502:physiology*; D005419:Flavonoids / Q000494:pharmacology; D053506:Matrix Metalloproteinase 10 / Q000096:biosynthesis / Q000235:genetics; D053507:Matrix Metalloproteinase 11 / Q000096:biosynthesis / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis* / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D019311:Staurosporine / Q000494:pharmacology
D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D005419:Flavonoids; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; C061779:endothelin 1, Ala(1,3,11,15)-; D053507:Matrix Metalloproteinase 11; D019278:Matrix Metalloproteinase 3; D053506:Matrix Metalloproteinase 10; D019311:Staurosporine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one