Angiotensin (A I, A II, A III) receptor characterization. Correlation of prostaglandin release with peptide degradation

• Published in: Circulation research 1977-08, Vol.41 (2), p.154-158
• Main Authors: Blumberg, A L, Nishikawa, K, Denny, S E, Marshall, G R, Needleman, P
• Format: Article
• Language: English
• Subjects: Angiotensin II - analogs & derivatives; Angiotensin II - antagonists & inhibitors; Angiotensin II - metabolism; Angiotensin II - pharmacology; Angiotensin III - antagonists & inhibitors; Angiotensin III - metabolism; Angiotensin III - pharmacology; Angiotensin Receptor Antagonists; Animals; Biological Assay; Chromatography, Thin Layer; Dose-Response Relationship, Drug; Kidney - metabolism; Male; Mesenteric Arteries - metabolism; Methods; Perfusion; Prostaglandins E - analysis; Prostaglandins E - metabolism; Rabbits; Receptors, Angiotensin; Receptors, Cell Surface
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.41.2.154

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.