Interaction of synthetic sarafotoxin with rat vascular endothelin receptors.
The effects of synthetic analogs of sarafotoxin (STX) S6b, a snake venom peptide with a high sequence homology to the endothelium-derived vasoconstrictor endothelin (ET), on ET receptor binding activity and cytosolic free Ca2+ concentration [( Ca2+]i) were studied in cultured rat vascular smooth muscle cells. Binding studies revealed that [Cys1-15, Cys3-11] STX competed with 125I-ET for the binding to its vascular receptors with lower affinity than that of ET, but was far more effective than [Cys1-11, Cys3-15]STX in inhibiting the binding. [Cys1-15, Cys3-11]STX had a less potent effect on increasing [Ca2+]i than ET, whereas [Cys1-11, Cys3-15]STX was inactive. These data suggest that there may exist heterogenous subpopulations of the vascular ET/STX receptors, and that the proper double cyclic structure of STX is essential for interacting with its putative receptors to induce the [Ca2+]i response.
Hirata
Y
Y
Department of Medicine, Tokyo Medical and Dental University, Japan.
Yoshimi
H
H
Marumo
F
F
Watanabe
T X
TX
Kumagaye
S
S
Nakajima
K
K
Kimura
T
T
Sakakibara
S
S
D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured; D004220:Disulfides; D004730:Endothelium, Vascular / Q000378:metabolism*; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents / Q000378:metabolism / Q000494:pharmacology*; D014757:Viper Venoms / Q000138:chemical synthesis / Q000494:pharmacology*
D004220:Disulfides; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6