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  • Title: Evidence for phosphoramidon-sensitive conversion of big endothelin-1 to endothelin-1 in isolated rat mesenteric artery.
    Author: Hisaki K, Matsumura Y, Ikegawa R, Nishiguchi S, Hayashi K, Takaoka M, Morimoto S.
    Journal: Biochem Biophys Res Commun; 1991 Jun 28; 177(3):1127-32. PubMed ID: 2059203.
    Abstract:
    The effect of phosphoramidon, a metalloproteinase inhibitor, on the pressor response to big endothelin-1 (big ET-1) in the isolated perfused rat mesenteric artery was examined. Big ET-1 (10(-9)-10(-7) M) caused a concentration-dependent increase in the perfusion pressure. The pressor response was markedly suppressed by phosphoramidon (10(-5) M). The inhibitor did not influence the ET-1 (5 X 10(-11)-10(-8) M)-induced pressor action. Big ET-1 (5 X 10(-8) M)-induced pressor action was accompanied by an increase in immunoreactive (IR)-ET in the perfusate, and this increase was suppressed by the addition of phosphoramidon. IR-ET in the perfusate was confirmed to be ET-1, as determined by reverse-phase HPLC. These findings strongly suggest that phosphoramidon-sensitive metalloproteinase contributes to the conversion of big ET-1 to ET-1, in vivo.
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