SARAFOTOXIN S6C : AN AGONIST WHICH DISTINGUISHES BETWEEN ENDOTHELIN RECEPTOR SUBTYPES

Abstract In contrast to endothelin-1 (ET-1) and several of its analogues, sarafotoxin S6c (S6c) was a much more potent inhibitor of [ 125 I]-ET-1 binding in rat hippocampus and cerebellum (K i ∼ 20 pM) than in rat atria and aorta (K i ∼ 4500 nM), suggesting the existence of ET-1 receptor subtypes (aorta/atria, ET A ; hippocampus/cerebellum, ET B ). S6c was a potent activator of PI turnover in hippocampus (EC 50 ∼ 10 nM) but not atria (EC 50 > 1 μM), unlike ET-1 which was active in both tissues. S6c, therefore, is a highly selective ET B agonist. Furthermore, S6c was a potent pressor agent in the pithed rat (ED 25 mm Hg ≈ 0.1 nmoles/kg, i.v.), suggesting that the ET B receptor subtype may be important in cardiovascular function.