Effect of phosphoramidon on big endothelin-2 conversion into endothelin-2 in human renal adenocarcinoma (ACHN) cells. Analysis of endothelin-2 biosynthetic pathway.
The biosynthetic pathway of endothelin (ET)-2 was analyzed in cultured ACHN cells. In the supernatant, we detected three ET-2-related peptides, ET-2, big ET-2(1-38) and big ET-2(22-38). Phosphoramidon decreased the amount of ET-2 and increased that of big ET-2(1-38) dose-dependently. The amount of big ET-2(1-37) did not significantly change. These results suggest that big ET-2 is composed of 38 and not 37 amino acid residues, and that a putative ET-2-converting enzyme (ECE-2) should be classified as a phosphoramidon-sensitive neutral metalloprotease, bearing a resemblance to the putative ET-1-converting enzyme (ECE-1) in endothelial cells.
Yorimitsu
K
K
Third Department of Internal Medicine, School of Medicine, Chiba University, Japan.
Shinmi
O
O
Nishiyama
M
M
Moroi
K
K
Sugita
Y
Y
Saito
T
T
Inagaki
Y
Y
Masaki
T
T
Kimura
S
S
D000230:Adenocarcinoma; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003429:Cross Reactions; D019332:Endothelin-1; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000096:biosynthesis* / Q000378:metabolism; D006020:Glycopeptides / Q000494:pharmacology*; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism*; D008666:Metalloendopeptidases; D011498:Protein Precursors / Q000378:metabolism; D011863:Radioimmunoassay; D014407:Tumor Cells, Cultured
D019332:Endothelin-1; D016232:Endothelins; D006020:Glycopeptides; D011498:Protein Precursors; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C000606923:ECE1 protein, human; C000606924:ECE2 protein, human; D000072396:Endothelin-Converting Enzymes; C008890:phosphoramidon