Endothelin-3 can both facilitate and inhibit transmitter release in the guinea-pig vas deferens.

Endothelin-3 (10 nM) produced a significant facilitation of the release of ATP from the in vitro guinea-pig vas deferens. This effect was converted to an inhibition of release by pretreatment with BQ-123, cyclo-(D-Trp,D-Asp,L-Pro,D-Val,L-Leu), an endothelin ETA receptor antagonist. Desensitization of endothelin ETB receptors by sarafotoxin S6c antagonized, but did not reverse, the facilitatory effect of endothelin-3. The release of noradrenaline was not facilitated by endothelin-3; however, following pretreatment with BQ-123 the release of noradrenaline was reduced by the peptide. These results indicate that there may be both facilitatory and inhibitory prejunctional endothelin receptors and further suggest that the release of the sympathetic nerve cotransmitters ATP and noradrenaline may be differentially modulated.