A human platelet angiotensin I-processing system. Identification of components and inhibition of angiotensin-converting enzyme by product

• Published in: The Journal of biological chemistry Vol. 260; no. 13; pp. 7857 - 7860
• Main Authors: Snyder, R A, Watt, K W, Wintroub, B U
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 05.07.1985; American Society for Biochemistry and Molecular Biology
• Subjects: Aminoacids, peptides. Hormones. Neuropeptides; Analytical, structural and metabolic biochemistry; Angiotensin I - analogs & derivatives; Angiotensin I - metabolism; Angiotensin-Converting Enzyme Inhibitors; Angiotensins - metabolism; Animals; Biological and medical sciences; Blood Platelets - enzymology; Chromatography, Gel; Chromatography, High Pressure Liquid; Fundamental and applied biological sciences. Psychology; Humans; Hydrogen-Ion Concentration; Iodoacetamide - pharmacology; Leupeptins - pharmacology; Lung - enzymology; Mersalyl - pharmacology; Molecular Weight; Proteins; Rabbits; Human; Platelet; Enzyme; Angiotensin converting enzyme; Peptide hormone; Inhibition; Angiotensin II; Metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(17)39531-5

Mechanisms controlling the local generation of angiotensin II by vascular tissue are incompletely understood. Human platelets were examined for their ability to metabolize angiotensin I. Platelet-dependent angiotensin I metabolism was detected by a high performance liquid chromatography assay which allowed quantitation of angiotensin I substrate utilized and products formed. The major product of platelet-dependent angiotensin I metabolism was identified as des-Leu10-angiotensin I. The platelet des-Leu10-angiotensin I-generating activity had a pH optimum of 6.0-6.5 and was inhibited 100% by mersalyl acid (10(-4) M), 86% by leupeptin (10(-4) M), and 95% by iodoacetamide (10(-2) M). The activity had an approximate Mr = 70,000 as determined by Sephacryl S-200 gel filtration. Intact human platelets stimulated with calcium ionophore (1-10 microM) released 13.7-30.8% of the des-Leu10-angiotensin I-generating activity. Des-Leu10-angiotensin I, the major product of platelet angiotensin I metabolism, inhibited human serum and purified rabbit lung angiotensin-converting enzymes with an I50 of 3.7 X 10(-6) and 2.0 X 10(-6) M, respectively. These results suggest that the platelet may control local angiotensin II formation at vascular sites both by metabolism of the precursor peptide angiotensin I and by generation of an endogenous angiotensin-converting enzyme inhibitor, des-Leu10-angiotensin I. This platelet-dependent pathway may contribute to the control of local levels of vasoactive peptides, such as bradykinin and angiotensin II, so as to alter local tissue blood flow.