SARAFOTOXIN-S6C - AN AGONIST WHICH DISTINGUISHES BETWEEN ENDOTHELIN RECEPTOR SUBTYPES

In contrast to endothelin-1 (ET-1) and several of its analogues, sarafotoxin S6c (S6c) was a much more potent inhibitor of [125I]-ET-1 binding in rat hippocampus and cerebellum (Ki ∼ 20 pM) than in rat atria and aorta (Ki ∼ 4500 nM), suggesting the existence of ET-1 receptor subtypes (aorta/atria, ETA; hippocampus/cerebellum, ETB). S6c was a potent activator of PI turnover in hippocampus (EC50 ∼ 10 nM) but not atria (EC50 > 1 μM), unlike ET-1 which was active in both tissues. S6c, therefore, is a highly selective ETB agonist. Furthermore, S6c was a potent pressor agent in the pithed rat (ED25 mm Hg ≈ 0.1 nmoles/kg, i.v.), suggesting that the ETB receptor subtype may be important in cardiovascular function. © 1991.