SUBTYPES OF ENDOTHELIN ET(A) AND ET(B) RECEPTORS MEDIATING VENOUS SMOOTH-MUSCLE CONTRACTION

In rabbit saphenous vein, endothelin (ET)-1 and ET-3 induced sustained contractions whereas the selective agonists of the ET(B) receptor, sarafotoxin S6c (STXc) and IRL 1620, induced transient contractions. In the presence of an ET(A) antagonist, BQ-123, contractions induced by ET-1, STXc and IRL 1620 did not change whereas ET-3 induced only transient contraction. The ET(B) antagonists, RES-701-1 and IRL 1038, only weakly antagonized the effects of these stimulants. In the muscle pretreated with STXc, neither STXc nor IRL 1620 was effective whereas ET-3 induced sustained contraction at higher concentrations than ET-1. In the muscle pretreated with STXc, BQ-123 weakly antagonized the effect of ET-1 and abolished the effect of ET-3. These results suggest that there are two types of ET receptors; less tachyphylactic and isopeptide-selective ET(A) receptor, and tachyphylactic and isopeptide-nonselective ET(B) receptor. The ET(A) receptors may be further classified as a BQ-123-sensitive ET(A1) and a BQ-123-insensitive ET(A2) subtypes. The ET(B) receptors may also be subclassified as the ET(B1) and ET(B2) subtypes based on the sensitivity to the ET(B) antagonists. (C) 1994 Academic Press, Inc.