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  • Title: Pharmacologic evidence for the specificity of the phosphoramidon-sensitive endothelin-converting enzyme for big endothelin-1.
    Author: Télémaque S, Gratton JP, Claing A, D'Orléans-Juste P.
    Journal: J Cardiovasc Pharmacol; 1993; 22 Suppl 8():S85-9. PubMed ID: 7510007.
    Abstract:
    The pharmacology of human big endothelin-1 (big ET-1) and big ET-3 was compared in five pharmacologic models: perfused rat and guinea pig lungs, perfused rabbit kidney, and in the rat and the guinea pig in vivo (blood pressure monitoring). In these models, big ET-1 consistently induced concentration- or dose-dependent pharmacologic effects sensitive to phosphoramidon (vasopressor or prostanoid-releasing effects). In contrast, big ET-3, dissolved in either phosphate-buffered saline (pH 7.4) or 0.1% acetic acid, was inactive in all the models used in this study. In addition, the activity of big ET-3 was also assessed in the prostatic portion of the rat vas deferens. In this model, although big ET-1 induced a phosphoramidon-sensitive increase of the twitch response of the tissue to electrical stimulation, big ET-3, dissolved either in phosphate-buffered saline or acetic acid, remained inactive. Our results, presented in the above-mentioned models, illustrate the capacity of the phosphoramidon-sensitive endothelin-converting enzyme (ECE) to discriminate between human big ET-1 and big ET-3.
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