Evidence for atypical endothelin receptors and for presence of endothelin-converting enzyme activity in the mouse isolated vas deferens.

The endothelin receptors controlling sympathetic neurotransmission and the presence of endothelin-converting enzyme were investigated in the mouse vas deferens. Endothelin-1 or endothelin-3 (0.01-100 nM) enhanced contractions evoked by field stimulation, yielding EC50 (geometric mean and 95% confidence limits) of 0.7 nM (0.4-1.6) and 13.7 nM (10.2-14.1) and Emax (mean +/- S.E.M. increase in twitch tension, in mg/10 mg wet tissue) of 473 +/- 35 and 520 +/- 51, respectively. The selective endothelin ETB receptor agonists IRL 1620 (Suc-[Glu9,Ala11,15]endothelin-1) and sarafotoxin S6c were inactive up to 100 nM. Responses to endothelin-3 were progressively inhibited by the selective endothelin ETA receptor antagonist BQ-123 (cyclo[D-Trp-D-Asp-Pro-D-Val-Leu]) (10, 30 and 100 nM). At 100 nM, BQ-123 almost abolished the response to endothelin-3 (100 nM). In contrast, at 100, 300 nM and 1 microM, BQ-123 shifted the curve to endothelin-1 to the right only 2-, 5- and 6-fold, respectively. The selective endothelin ETB receptor antagonist BQ-788 (N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methyl-leucyl-D-1-++ +methoxycarbonyltryptophanyl-D-norleucine) (100 nM) did not modify responses to endothelin-1 or endothelin-3 (0.01-100 nM). Big-endothelin-1 (0.3-30 nM) was 10-fold less potent than endothelin-1 in increasing neurogenic responses (EC50 6.8 nM, 4.7-9.6; Emax 457 +/- 37 mg/10 mg wet tissue). Preincubation with phosphoramidon (100 microM) reduced responses to big-endothelin-1, but not endothelin-1.(ABSTRACT TRUNCATED AT 250 WORDS)