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.