2 TYPES OF ENDOTHELIN-B RECEPTORS MEDIATING RELAXATION IN THE GUINEA-PIG ILEUM

In guinea pig ileum, binding assays showed the existence of endothelin (ET) receptors of ET(A) (isopeptide-selective) and ET(B) (nonselectiv e) subtypes. ETs induced relaxation followed by contraction. ET-I indu ced greater contraction at lower concentrations than ET-3. An ET(A) an tagonist, BQ-123, shifted the concentration-response curves for ETs to the right. An ET(B) antagonist, IRL 1038, shifted the concentration-r esponse curve for ET-3 to the right and downwards with little effect o n the curve for ET-1. In contrast, ET-1 and ET-3 induced relaxation at similar concentrations. The relaxation induced by ETs was composed of an initial transient relaxation followed by sustained relaxation. Onl y the transient phase was inhibited by IRL 1038 in a concentration-dep endent manner. These results suggest that the ET-induced relaxation is mediated by two types of ET(B) receptor; transient and sustained rela xations are mediated respectively by IRL 1038-sensitive and IRL 1038-i nsensitive subtypes of ET(B) receptor. In contrast, the contractile ef fect seems to be mediated mainly by the ET(A) receptor and partially b y an IRL 1038-sensitive subtype of ET(B) receptor.