RELEASE OF ADRENAL CATECHOLAMINES BY ANGIOTENSIN I

¹ Department of Pharmacology, University of Virginia, School of Medicine, Charlottesville, Virginia; Research Division, Cleveland Clinic, Cleveland, Ohio

A structure activity study was attempted to determine the optimum angiotensin (Ang) peptide chain length for adrenal medullary stimulation. Isolated cat adrenal glands were retrograde perfused at a flow rate of 1 ml/min with phosphate-buffered Locke's solution at 23-25°C. Continuous catecholamine analysis was performed with an automated trihydroxyindole procedure. All drugs were administered either by close single injection (0.05-0.1 ml) or by perfusion. Ang series peptides administered were His-Pro-Phe; Val-Tyr-Ileu-His-Pro-Phe; Arg-Val-Tyr-Ileu-His-Pro-Phe; 1-Aap(NH₂)-5-Val-Ang II; 1-Asp-5-Ileu Aug I and II; 1-Asp-5-Ileu-tetradecapeptide (renin substrate); 1-Asp-5-Ileu-8-Ala-Ang II. The optimum Ang chain length for adrenal medullary stimulation appeared to be 8 to 10 amino acids. There was cross-tachyphylaxis between the active peptides. Sustained catecholamine secretion was induced by administering the peptides via perfusion. Peptide-induced adrenal catecholamine secretion required Ca⁺⁺. Since Aug I is an extremely potent peptide, studies were performed with 1O-¹⁴C-Leu-Ang I or antibody for 1-Asp-5-Ileu-Ang II to determine if the decapeptide was acting indirectly through conversion to Ang II. Ang I was found to have a marked, direct effect on the isolated adrenal medulla.

This article has been cited by other articles:

				L. Oliveira, C. M. Costa-Neto, C. R. Nakaie, S. Schreier, S. I. Shimuta, and A. C. M. Paiva The Angiotensin II AT1 Receptor Structure-Activity Correlations in the Light of Rhodopsin Structure Physiol Rev, April 1, 2007; 87(2): 565 - 592. [Abstract] [Full Text] [PDF]

				C. Hsu, G Brooker, M. Peach, and T. Westfall Inhibition of catecholamine release by tolbutamide and other sulfonylureas Science, March 21, 1975; 187(4181): 1086 - 1087. [Abstract] [PDF]