The potassium channel opener BRL 38227 inhibits binding of [ 125I]-labelled endothelin-1 to rat cardiac membranes

Abstract

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.