title: Pharmacologic evidence for the specificity of the phosphoramidon-sensitive endothelin-converting enzyme for big endothelin-1.
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.
authors.affiliation: Department of Pharmacology, Medical School, Université de Sherbrooke, Québec, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Télémaque
authors.forename: J P
authors.initials: JP
authors.lastname: Gratton
authors.forename: A
authors.initials: A
authors.lastname: Claing
authors.forename: P
authors.initials: P
authors.lastname: D'Orléans-Juste
mesh_terms: D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015777:Eicosanoids / Q000378:metabolism; D004558:Electric Stimulation; D019332:Endothelin-1; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000494:pharmacology*; D011464:Epoprostenol / Q000378:metabolism; D005260:Female; D006020:Glycopeptides / Q000494:pharmacology*; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism; D008297:Male; D008666:Metalloendopeptidases; D011498:Protein Precursors / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects; D013379:Substrate Specificity; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D015777:Eicosanoids; D019332:Endothelin-1; D016232:Endothelins; D006020:Glycopeptides; D011498:Protein Precursors; D011464:Epoprostenol; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; C008890:phosphoramidon