Protein synthesis dependent effects of kinins on astrocyte prostaglandin synthesis.
It has been shown that kinins and their receptors are over expressed in the brain under pathophysiological conditions such as inflammation. However, little is known about the possible role of kinins, and especially bradykinin in brain inflammation. Although kinins are thought to have immediate effects, peptides may also exert longer and protein synthesis dependent actions. To evaluate this possibility, we assessed the regulation of prostaglandin E(2) synthesis after 15h bradykinin or Lys-des-Arg(9)-bradykinin (B(1) receptor agonist) treatment in rat neonatal astrocytes. Bradykinin, dose dependently stimulated basal and lipopolysaccharide-induced prostaglandin E(2) production, whereas exposure of astrocytes to the B(1) receptor agonist decreased both basal and lipopolysaccharide-induced prostaglandin E(2) release in a dose-dependent manner. These kinin effects on PGE(2) synthesis were completely abrogated by actinomycin-D and cycloheximide, suggesting de novo synthesis of proteins. Bradykinin also increased cyclooxygenase-2 protein levels about 2-fold, while the B(1) receptor agonist decreased cyclooxygenase-2 protein expression. There was no change in cyclooxygenase-1 protein levels after treatment with either of the kinins. Our data suggest a delayed feedback regulatory mechanism of kinins on astrocyte inflammation, whereby astrocyte prostaglandin synthesis is initially enhanced by bradykinin (B(2)) and eventually blocked by kinin breakdown product, acting on B(1) receptors. At least part of this presumed feedback loop could be mediated by de novo protein synthesis of cyclooxygenase-2.
Filipovich-Rimon
Talia
T
Department of Clinical Pharmacology, Ben-Gurion University of the Negev, POB 653, Beer-Sheva 84105, Israel.
Fleisher-Berkovich
Sigal
S
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1 / Q000819:agonists / Q000378:metabolism
D008070:Lipopolysaccharides; D011453:Prostaglandins; D011500:Protein Synthesis Inhibitors; D043783:Receptor, Bradykinin B1; D003609:Dactinomycin; D003513:Cycloheximide; D015232:Dinoprostone; D001920:Bradykinin