Cadmium directly acts on endothelin receptor and inhibits endothelin binding activity.
The binding of endothelin (ET) to human placenta ET receptor was strongly inhibited by cadmium ions (Cd2+) (IC50 = 2 x 10(-5) M). Experiments with affinity cross-linking showed that the major 40 kDa receptor was inhibited to form a [125I]ET-1/receptor complex. The mode of inhibition was noncompetitive with respect to ET-1. The inhibitory effect of Cd2+ on solubilized ET receptor was partially reversed by the chelating agent, ethylenediaminetetraacetic acid (EDTA), whereas the effect was irreversible for the membrane-associated receptor. The rat aorta contractions by ET were prevented by pretreatment or addition of Cd2+.
Wada
K
K
Department of Molecular Genetics, Nippon Roche Research Center, Kamakura, Japan.
Fujii
Y
Y
Watanabe
H
H
Satoh
M
M
Furuichi
Y
Y
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002104:Cadmium / Q000494:pharmacology*; D002413:Cations, Divalent / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D016232:Endothelins / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008297:Male; D010920:Placenta; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000187:drug effects*; D017466:Receptors, Endothelin; D014661:Vasoconstriction / Q000187:drug effects
D002413:Cations, Divalent; D016232:Endothelins; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D002104:Cadmium; D004492:Edetic Acid