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

The authors examined the ability of the angiotensins (A I, A II, A III) to release a prostagldnin 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> A III>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>A II>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 (K(B)) of the competitive angiotensin antagonists [Ile⁷]-A III and [Sar¹, Ile⁸]-A II were determined with each angiotensin. K(B) values of the individual antagonists 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.