The potassium channel opener BRL 38227 inhibits binding of [125I]-labelled endothelin-1 to rat cardiac membranes.
Binding of [125I]-labelled endothelin-1 (ET-1) to rat cardiac membranes and the effects of endothelin-1 (ET-1), endothelin-3 (ET-3), the calcium channel antagonist nifedipine, and both enantiomers of the potassium channel opener cromakalim (BRL 34915) on binding have been examined. Specific binding of [125I]-ET-1 was inhibited in a concentration dependent manner by both unlabelled ET-1 (10(-12)-10(-7) M) and ET-3 (10(-12)-10(-6) M). Nifedipine (10(-11)-10(-5) M) did not affect [125I]-ET-1 binding. However, BRL 38227 (10(-11)-10(-5) M), the biologically active isomer of cromakalim, significantly inhibited [125I]-ET-1 binding. The inactive isomer, BRL 38226 (10(-11)-10(-5) M) had no effect. These findings provide the first evidence for a stereospecific interaction between BRL 38227 and an ET-1 binding site in rat cardiac membranes.
Waugh
C J
CJ
Edinburgh University Department of Medicine, Western General Hospital.
Dockrell
M E
ME
Haynes
W G
WG
Olverman
H J
HJ
Williams
B C
BC
Webb
D J
DJ
D000818:Animals; D001578:Benzopyrans / Q000378:metabolism* / Q000494:pharmacology; D001667:Binding, Competitive; D019806:Cromakalim; D016232:Endothelins / Q000378:metabolism*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D012508:Sarcolemma / Q000378:metabolism*
D001578:Benzopyrans; D016232:Endothelins; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D009543:Nifedipine