The Characteristics of Endothelin Receptor Subtypes on Muscle Contraction and Neuro-transmission in Rat Vas Deferens

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We observed encothelin (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 ET_B-receptor agonists, IRL 1620 and safafotoxin S6c, produced only a small contraction or no contraction at a concentration of 1 μM. The rank order of contraction potencies (pD_2 value) was ET-1=ET-2>ET-3<Gt>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 ET_A receptor antagonist, and BQ-788 (1 μM), a selective ET_B receptor antagonist. The contractile responses to ET-1 were antagonized by pretreatment with BQ-123 (10 μM), but not with BQ-788 (1 μM). 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 μM) and BQ-788 (1 μM). The ET-1-induced facilitation was antagonized by pretreatment with BQ-123 (3 μM), but not with BQ-788 (10 μM). These results suggest that in rat vas deferens the ET_A receptors are divided into BQ-123-sensitive ET_<A1> and BQ-123-insensitive ET_<A2> subtypes, and the production of a contractile response of smooth muscle as well as the facilitation of neurotransmission are accomplished through mediation by ET_<A1>-and ET_<A2>-subtypes.
1998-07-15

The Characteristics of Endothelin Receptor Subtypes on Muscle Contraction and Neuro-transmission in Rat Vas Deferens

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