Characteristics of bradykinin and TPA increases in the PGE2 levels of human urothelial cells.
Prostaglandins play a potential key role in the pathogenesis of urinary bladder cancer. Bradykinin and TPA increases in prostaglandin (PG)E2 levels were compared in primary cultures of human urothelial cells. Increased PGE2 levels were dependent upon the dose of TPA and were not apparent until 30-60 min after addition of TPA, with larger increases occurring between 60 and 120 min. Stimulation was inhibited by cycloheximide. Addition of arachidonic acid to TPA-stimulated cells increased PGE2 to a level similar to that seen in arachidonic acid-stimulated controls, and this level was not altered by cycloheximide. In contrast to TPA, the bradykinin-increased PGE2 levels were maximal at 5 min (the earliest time-point assessed) and were not inhibited by cycloheximide. Increases in PGE2 levels by both TPA and bradykinin required calcium. Excessive stimulation by TPA resulted in a desensitization to subsequent stimulation by TPA, but not bradykinin. Combination of TPA with bradykinin produced at least an additive effect on PGE2 levels. Both agonists increased the release of [3H]arachidonic acid over a time-course similar to their PGE2 response. Bradykinin and TPA appear to increase PGE2 levels by enhancing arachidonic acid availability through separate phospholipase pathways. Thus, human urothelial cells exhibit similar, but yet distinct profiles for prostaglandin stimulation by TPA and bradykinin.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D011458:Prostaglandins E / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014513:Ureter / Q000166:cytology / Q000378:metabolism*
D001095:Arachidonic Acids; D011458:Prostaglandins E; D016718:Arachidonic Acid; D003513:Cycloheximide; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D001920:Bradykinin; D002118:Calcium