PROSTACYCLIN PRODUCTION BY PERTURBED BOVINE AORTIC ENDOTHELIAL-CELLS IN CULTURE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 64  (4) , 801-806
Abstract
This study reports that endotoxin (Escherichia coli serotype O26:B6) and 12-0-tetradecanoyl-phorbol-13-acetate stimulate cultured bovine aortic endothelial cells to generate prostacyclin. The prostacyclin concentration of the culture medium was measured indirectly by radioimmunoassay for 6-keto-PGF1.alpha. [6-keto-prostaglandin F1.alpha.]. The amount of prostacyclin generated depended on the concentration of endotoxin or phorbol diester. Prostacyclin generation was not immediate, but occurred slowly after a 6 h lag period. The perturbed cells contracted and showed marked shape changes that correlated temporally with the start of enhanced prostacyclin production. Cytochalasins B and D, vinblastine and colchicine inhibited prostacyclin production, indicating involvement of the cytoskeleton in the cellular response to endotoxin and phorbol diester. The increase in prostacyclin production was prevented by trifluoperazine, an inhibitor of the Ca2+-calmodulin system, which is known to be involved in cytoskeletal function. Generation of prostacyclin was inhibited by cycloheximide and actinomycin D, indicating dependence on protein and RNA synthesis. Exposure to endotoxin or phorbol diester leads, via a series of reactions that involve RNA and protein synthesis and require intact cytoskeletal function, to the generation of toxic active intermediate(s) that stimulate the enyzmes necessary for prostacyclin production.

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