Aa. Almotrefi et al., EFFECTS OF AMIODARONE ON OUABAIN BINDING TO MICROSOMAL NA-ATPASE IN GUINEA-PIG HEART PREPARATIONS(, K+), General pharmacology, 29(4), 1997, pp. 639-643
1. The influence of amiodarone on [H-3]ouabain (OUA) binding to myocar
dial Na+, K+-ATPase was studied at various KCl concentrations in guine
a pig heart microsomal preparations to test the hypothesis that the dr
ug acts on the same receptor sites as cardiac glycosides. 2. First, a
series of assays for OUA binding to Na+, K+-ATPase were performed in t
he range of 64-800 nM at 2.5, 5.0 and 10.0 mM K+ concentration. The dr
ug exhibited increasing binding tendency with increasing concentration
s and elevation in K+ levels, 3. Competitive binding assays were then
performed at 256, 512 and 800 nM OUA in the presence of 50, 100 and 20
0 mu M amiodarone at 5.0 mM KCl, respectively. At each OUA concentrati
on, a concentration-dependent left to-right shift was observed in the
binding affinity with increasing amiodarone concentration. Similar ass
ays at 2.5 and 10.0 mM K+ showed the same trends. These effects were s
ignificant for 200 mM amiodarone at all K+ levels and OUA concentratio
ns. 4. Furthermore, different OUA concentrations were also shown to di
splace amiodarone in a concentration-dependent fashion. 5. These resul
ts indicate that amiodarone competes with OUA for specific binding sit
es on myocardial microsomal Na+, K+-ATPase. They lead to the conclusio
n that myocardial Na+, K+-ATPase is a possible receptor for some of th
e cardiac actions of amiodarone, such as its proarrhythmic effects. (C
) 1997 Elsevier Science Inc.