Angiotensin (A I, A II, A III) receptor characterization. Correlation of prostaglandin release with peptide degradation.
We examined the ability of the angiotensins (A I, A II, A III) to release a prostaglandin E (PGE)-like substance in the isolated Krebs' perfused kidney and mesenteric vasculature of the rabbit by parallel bioassay. In the kidney, the order of potency for PGE release was A II greater than A III greater than A I with ED50's of 36, 100, and 500 pmol, respectively. In the mesenteric preparation, on the other hand, the order of potency was A III greater than A II greater than A I with ED50's of 75, 125, and 500 pmol, respectively. During one transit through the kidney 72-76% of bioassayable A I and A II was degraded. A III was 89% metabolized. In contrast, the mesenteric vasculature inactivated only 27% of A II and 23% of A III. This data suggests an inverse relationship between renal peptide degradation and PGE release. For characterization of the renal angiotensin receptor-mediating PGE release, dissociation constants (KB) of the competitive angiotensin antagonists [IIe7]-A III and [Sar1, IIe3]-A II were determined with each angiotensin. KB values of the individual antaganists were not significantly different with A I, A II, or A III; this finding suggests that one renal angiotensin receptor is involved with PGE release.
D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D000805:Angiotensin III / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001681:Biological Assay; D002855:Chromatography, Thin Layer; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism*; D008722:Methods; D010477:Perfusion; D011458:Prostaglandins E / Q000032:analysis / Q000378:metabolism*; D011817:Rabbits; D011945:Receptors, Angiotensin; D011956:Receptors, Cell Surface
D057911:Angiotensin Receptor Antagonists; D011458:Prostaglandins E; D011945:Receptors, Angiotensin; D011956:Receptors, Cell Surface; D000804:Angiotensin II; D000805:Angiotensin III