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 releas e of ATP from the in vitro guinea-pig vas deferens. This effect was co nverted to an inhibition of release by pretreatment with BQ-123, cyclo -(D-Trp,D-Asp,L-Pro,D-Val,L-Leu), an endothelin ET(A) receptor antagon ist. Desensitization of endothelin ET(B) receptors by sarafotoxin S6c antagonized, but did not reverse, the facilitatory effect of endotheli n-3. The release of noradrenaline was not facilitated by endothelin-3; however, following pretreatment with BQ-123 the release of noradrenal ine 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 cotrans mitters ATP and noradrenaline may be differentially modulated.