Structure-activity relationships of α-human or rat atrial natriuretic polypeptide (α-hANP or α-rANP) and their analogs

• Published in: Japanese Journal of Pharmacology 1986, Vol.40 (suppl), p.77-77
• Main Authors: Yujiro Hayashi, Fuyuki Iwasa, Mayumi Furuya, Yasushi Kanai, Yoshiharu Minamitake, Ichiro Kubota, Norio Ohnuma, Kenji Kangawa, Hisayuki Matsuo
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

Recent autoradiographic studies indicate that ANP receptors are distributed on the glomeruli and vasa recta of the outer medulla in the rat kidney. We report here the structure activity relationships of α-hANP, α-rANP and their analogs as their receptor binding (B-A) and cyclic GMP (cGMP) producing (G-A) activities in rat glomeruli. N-terminal truncation of one to six residues of α-hANP or α-rANP resulted in slight changes in both activities. N-terminal elongation to α-rANP (γ-rANP) decreased B-A rather than G-A. On the other hand. C-terminal deletion of two residues (-Arg^27 -Tyr^28 ) markedly reduced these activities. Reduction in the activity of (Met(O)^12 )-α-hANP is greater in G-A than B-A. Infusion of (Met(O)^12 )-α-hANP into the rat renal artery evoked a diuresis comparable to α-hANP at 40 times dosage. This suggests that the hydrophobic residue at position 12 is not absolutely required for diuretic activity. Further, we could demonstrate that a physiological concentration (4×10^-10 M) of α-rANP stimulated cGMP generation when the appropriate conditions were set, while it has been reported that a relatively high concentration (10^-7 -10^-6 M) is required for the enhancement of cGMP production. This fact suggests that cGMP participates in ANP action on the renal glomeruli.