Presence of a phosphoramidon-sensitive endothelin-converting enzyme which converts big-endothelin-1, but not big-endothelin-3, in the rat vas deferens.
Endothelin-1 (ET-1) enhanced field stimulation-evoked (0.1 Hz), nerve-mediated contractions of the prostatic portion of the rat vas deferens. The human precursor of ET-1, big-endothelin (1-38) (big-ET-1) was only two-fold less potent than ET-1 (pD2 values: 7.30 and 7.49, respectively). The threshold concentrations necessary to elicit an increase of the response to electrical stimulation was lower for ET-1 (5 nmol/l) than for big-ET-1 (25 nmol/l). Endothelin-3 (ET-3) also markedly enhanced the response of the tissue to field stimulation with a potency similar to ET-1 (pD2 value: 7.59). In contrast, the precursor of ET-3, big-endothelin (1-41) (big-ET-3), was inactive at concentrations up to 0.5 mumol/l. Treatment of the preparations with phosphoramidon (50 mumol/l) markedly reduced the twitch enhancement by big-ET-1 without affecting the response to ET-1. Our results suggest the presence of a specific phosphoramidon-sensitive endothelin-converting enzyme which converts big-ET-1 to ET-1 in the rat vas deferens.
Télémaque
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Department of Pharmacology, School of Medicine, University of Sherbrooke, Quebec, Canada.
D'Orléans-Juste
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D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004558:Electric Stimulation; D019332:Endothelin-1; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000378:metabolism*; D006020:Glycopeptides / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008666:Metalloendopeptidases; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D011498:Protein Precursors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014649:Vas Deferens / Q000201:enzymology* / Q000502:physiology
D019332:Endothelin-1; D016232:Endothelins; D006020:Glycopeptides; D011498:Protein Precursors; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; C008890:phosphoramidon