title: Mechanism of enhanced renal prostaglandin biosynthesis in ureter obstruction. Role of de novo protein synthesis.
abstract: Perfusion of a rabbit kidney 72 h after ureter obstruction resulted in a progressive increase in bioassayable prostaglandin-like substances released in response to a fixed dose of bradykinin with time. Contralateral or normal kidneys showed no progressive increase with time of prostaglandin-like substances released in response to the same dose of agonist during perfusion. Actinomycin D, an inhibitor of RNA synthesis and cycholeximide, reversibly blocked the time-dependent progressive increase in renal prostaglandin-like substances released from the obstructed kidney. Acetylsalicylic acid, which covalently acetylates the cyclooxygenase, inhibited initial bradykinin-stimulated prostaglandin biosynthesis by 95% in the ureter-obstructed kidney, but within 60 to 90 min of perfusion there was progressive bioassayable prostaglandin E2 release in response to bradykinin which paralleled the non-aspirin-treated control. In the aspirin-treated contralateral (unobstructed control) and normal kidneys bradykinin-stimulated release of prostaglandin-like substances was inhibited by 85% and did not recover during the perfusion experiments consistent with the evidence that the control kidneys are not synthesizing new enzyme. These experiments suggest that the progressive enhanced prostaglandin release to fixed bradykinin doses in the ureter-obstructed kidney is dependent on de novo cyclooxygenase synthesis.
mesh_terms: D000818:Animals; D001681:Biological Assay; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis*; D014176:Protein Biosynthesis / Q000187:drug effects; D011817:Rabbits; D014513:Ureter / Q000502:physiology*
chemical_list: D011453:Prostaglandins; D011458:Prostaglandins E; D003609:Dactinomycin; D003513:Cycloheximide