Inactivation of endothelin-1 by an enzyme of the vascular endothelial cells.

• DOI: 10.1161/01.hyp.21.6.925
• Publication Date: 2012-06-12T00:24:03Z
• Authors: H L Jackman; P W Morris; S F Rabito; G B Johansson; R A Skidgel; E G Erdös
• Keywords: Diisopropyl fluorophosphate

We previously investigated the inactivation of endothelin-1 by deamidase (lysosomal protective protein), present in many cells, including vascular smooth muscle cells. This enzyme, which we originally purified from human platelets, preferentially hydrolyzes peptides at C-terminus with hydrophobic amino acids P1 or P1' position both and thereby inactivates endothelin-1, has a C-terminal sequence Ile19-Ile20-Trp21-OH. tested for presence cultured bovine aortic endothelial The final supernatant homogenized cells (S3) cleaved substrate dansyl-Phe-Leu-Arg rate 1.3 nmol/min per 10(6) pH 5.5 37 degrees C. Endothelin-1 was completely inactivated S3 fraction as determined on rat thoracic aorta strips. major site Ile20-Trp21 bond, established high performance liquid chromatography acid analysis where main product des-Trp21-endothelin-1. hydrolysis (5.9 milligram protein 23 C) blocked mainly inhibitors deamidase, diisopropyl fluorophosphate, but not some other peptidases. is first report novel pathway metabolism Thus, besides being source contain an enzyme that it.