Phosphoramidon inhibits the generation of endothelin‐1 from exogenously applied big endothelin‐1 in cultured vascular endothelial cells and smooth muscle cells

FEBS Letters

Matsumura, Yasuo¹  Takaoka, Masanori¹  Morimoto, Shiro¹  Ikegawa, Ruriko¹  Tsukahara, Yaeko¹ 

[1] Department of Pharmacology, Osaka University of Pharmaceutical Sciences, 2-10-65 Kawai, Matsubara, Osaka 580, Japan

关键词: Endothelin-1;    Big endothelin-1;    Metalloproteinase;    Phosphoramidon;    Endothelial cell;    Vascular smooth muscle cell;   

DOI  :  10.1016/0014-5793(91)81149-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

When cultured porcine aortic endothelial cells (ECs) were incubated with porcine big endothelin-1 (bit ET-I_1–39), there was a time-dependent increase in immunoreactive (IR)-ET in the culture supernatant, in addition to an endogenous IR-ET release fron the cells. Reverse-phase HPLC of the culture supernatant revealed one major IR-ET component corresponding to the elution position of synthetic ET-1, thereby indicating that the additional increase in IR-ET was due to the conversion of big ET-1 to mature ET-1_1–21. Phosphoramidon, a metalloproteinase inhibitor, strongly suppressed this increase in IR-ET as well as the endogenous IR-ET release. Cultured vascular smooth muscle cells (VSMCs) also released IR-ET. The apparent conversion of exogenously applied big ET-1 to ET-1 and its inhibition by phosphoramidon were observed using cultured VSMCs, although the enzyme inhibitor did not influence the basal secretion of IR-ET from VSMCs. These results suggest that both cultured ECs and VSMCs can generate ET-1 from exogenously applied big ET-1 via action of the same type of phosphoramidon-sensitive metalloproteinase, which is also involved in the endogenous ET-1 generation in ECs.

【 授权许可】

Unknown