Endothelin-1 production and endothelin converting enzyme expression by guinea pig airway epithelial cells.

Significant amount of endothelin-1 (ET-1) production and endothelin converting enzyme (ECE) activity have been detected in cultured guinea pig airway epithelial cells. Subsequent screening of the cDNA library constructed from epithelial cells, a complete cDNA of guinea pig ECE and a partial cDNA encoding preproET-1 were newly isolated. The production of ET-1 from epithelial cells was influenced by some vasoactive or inflammatory mediators, especially LPS enhances ET-1 production. Northern blot analysis revealed that mRNA level of ET-1 was increased in the LPS stimulated epithelial cells, but the effect on the ECE mRNA expression was obscure. These data suggest that the ET-1 production in the airway epithelial cells is regulated by the level of ET-1 mRNA expression with a constitutive manner, and the level of ECE, which act at a key biosynthetic step of the conversion of big ET-1 to ET-2, seems not to make a major contribution to the regulation of ET-1 release.