Evidence for phosphoramidon-sensitive conversion of big endothelin-1 to endothelin-1 in isolated rat mesenteric artery.
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.
Hisaki
K
K
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Matsumura
Y
Y
Ikegawa
R
R
Nishiguchi
S
S
Hayashi
K
K
Takaoka
M
M
Morimoto
S
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D019332:Endothelin-1; D016232:Endothelins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D006020:Glycopeptides / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010477:Perfusion; D011498:Protein Precursors / Q000378:metabolism / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D019332:Endothelin-1; D016232:Endothelins; D006020:Glycopeptides; D011498:Protein Precursors; C008890:phosphoramidon