Molecular Pharmacology, Vol 10, 57-67, Copyright © 1974 by the American Society for Pharmacology and Experimental Therapeutics

Enhancement of the Activity of Angiotensin II by Certain Cations

GASTON SCHAECHTELIN ¹, RODERICH WALTER ¹, HANS SALOMON ¹, JÍI JELÍNEK ¹, PETR KAREN ¹, and JOSEPH H. CORT ¹

¹ Laboratory for Peptide Biology, Institute of Organic Chemistry and Biochemistry, and Institute of Physiology, Academy of Sciences, Prague 4, Czechoslovakia; Department of Physiology and Biophsics, Mount Sinai School of Medicine of the City University of New York, New York 10029; and Institut de Pharmacologie, Université de Lausanne, 1011 Lausanne, Switzerland

Angiotensin II activity, as determined in the rat pressor and rat uterotonic assay systems, was found to be cation-sensitive. Na⁺ and Li⁺, studied in a concentration range from 1.5 to 470 mM, had similar enhancing effects on the activity of the peptide. The enhancement was nonlinear, with three inflection points giving rise to plateaus between concentrations of 5 and 50 mM salt, and above 150 mM. NH₄⁺ was about 50% as effective as Na⁺ in enhancing the pressor activity of angiotensin II, but Ca⁺⁺ was about twice as effective as Na⁺. The results with K⁺ were uncertain. As judged on the basis of studies with Na⁺, the enhancement was reversible and independent of the anion. Glucose and urea failed to enhance the activity of angiotensin II. It is suggested that an increase in the concentration of certain cations induces conformational changes in angiotensin II, leading to biologically more active structures.

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ACKNOWLEDGMENTS We thank Ms. Itka Pravdová for technical assistance and Ms. P. L. Hoffman for editorial help. We are grateful to Dr. H. Bein, Ciba-Geigy, Basel, Switzerland, and to Drs. A. J. Plummer and W. E. Wagner, Ciba-Geigy, Summit, N. J., for their generous gift of angiotensin II.