The characteristics of endothelin receptor subtypes on muscle contraction and neuro-transmission in rat vas deferens

We observed endothelin (ET)-induced contractile responses on prostatic and epididymal segments, as well as the facilitation of an electrically stimulated tone on prostatic segments of isolated rat vas deferens, In both segments, the selective ETB-receptor agonists, IRL 1620 and sarafotoxin S6c, produced only a small contraction or no contraction at a concentration of 1 mu M. The rank order of contraction potencies (pD(2) value) was ET-1=ET-2>ET-3 much greater than sarafotoxin S6c=IRL 1620, The maximum responses of ET-induced contractions in the prostatic segments were larger than those in the epididymal segments. The contractile response to ET-3 was antagonized by pretreatment for 30 min with BQ-123 (10 nM), a selective ETA receptor antagonist, and BQ-788 (1 mu M), a selective ETB receptor antagonist. The contractile responses to ET-1 were antagonized by pretreatment with BQ-123 (10 mu M), but not with BQ-788 (1 mu M). The ET-3-induced facilitation on the twitch response to electrical stimulation in the prostatic segment of the vas deferens was antagonized by BQ-123 (0.1 mu M) and BQ-788 (1 mu M). The ET-1-induced facilitation was antagonized by pretreatment with BQ-123 (3 mu M), but not with BQ-788 (10 mu M). These results suggest that in rat vas deferens the ETA receptors are divided into BQ-123-sensitive ETA1 and BQ-123-insensitive ETA2 subtypes, and the production of a contractile response of smooth muscle as well as the facilitation of neurotransmission are accomplished through mediation by ETA1- and ETA2-subtypes.