Phosphoramidon inhibition of the in vivo conversion of big endothelin‐1 to endothelin‐1 in the human forearm

• Published in: British journal of pharmacology 1995-09, Vol.116 (2), p.1821-1828
• Main Authors: Plumpton, Christopher, Haynes, William G., Webb, David J., Davenport, Anthony P.
• Format: Article
• Language: English
• Subjects: Adult; big endothelin; Biological and medical sciences; Blood vessels and receptors; Brachial Artery - metabolism; Endothelin; endothelin converting enzyme; Endothelins - blood; Endothelins - metabolism; Forearm - physiology; Fundamental and applied biological sciences. Psychology; Glycopeptides - pharmacology; human brachial artery; Humans; Male; phosphoramidon; Protease Inhibitors - pharmacology; Radioimmunoassay; selective solid‐phase extraction; Time Factors; vasoconstriction; Vertebrates: cardiovascular system; Volunteers
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1995.tb16669.x

1 The vasoconstrictor peptide, endothelin‐1 (ET‐1) and a biologically inactive C‐terminal fragment (CTF) are generated from an intermediate big ET‐1 by a putative ET converting enzyme, sensitive to phosphoramidon. We have developed a procedure using selective solid‐phase extraction and specific radioimmunoassays to measure the levels of immunoreactive (IR) big ET‐1 and the products of conversion (ET‐1 and CTF) in human plasma. These techniques have been used to determine the levels of the three peptides in venous plasma following local infusions of ET‐1 and big ET‐1, both alone and together with phosphoramidon 2 Infusion of ET‐1 into the brachial artery (5 pmol min−1) significantly increased (P