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 approximately 20 pM) than in rat atria and aorta (Ki approximately 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 approximately 10 nM) but not atria (EC50 greater than 1 microM), 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 approximately 0.1 nmoles/kg, i.v.), suggesting that the ETB receptor subtype may be important in cardiovascular function.
Williams
D L
DL
Department of New Lead Pharmacology, Merck Sharp & Dohme Research Laboratories, West Point, PA 19486.
Jones
K L
KL
Pettibone
D J
DJ
Lis
E V
EV
Clineschmidt
B V
BV
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001665:Binding Sites; D001667:Binding, Competitive; D001794:Blood Pressure / Q000187:drug effects; D002531:Cerebellum / Q000378:metabolism; D016232:Endothelins / Q000378:metabolism*; D006325:Heart Atria / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007679:Kidney Medulla / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D017466:Receptors, Endothelin; D014757:Viper Venoms / Q000378:metabolism / Q000494:pharmacology*
D016232:Endothelins; D010716:Phosphatidylinositols; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D014757:Viper Venoms; C057354:sarafotoxins s6