COMPETITIVE-INHIBITION OF (NA K)-ATPASE BY FURYLETHYLENES WITH RESPECT TO POTASSIUM-IONS/

The effects of newly synthetized derivatives of furylethylene: i) (5-n itro-2-furyl)-2-phenylsulfonyl-2-furylcarbonyl ethylene (FE1), ii) 1-( 5-phenylsulfonyl-2-furyl)-2-phenylsulfonyl- 2-furylcarbonyl ethylene ( FE2), iii) sulfonyl-2-furyl)-2-phenylsulfonyl-2-tienocarbonyl ethylene (FE3), on the reaction kinetics of the dog kidney (Na/K)-ATPase were tested. Besides the conjugated triene moiety of the furylethylene skel eton, the groups responsible for the reaction with nucleophilic groups , the formyl group that connects the second furyl ring in FE1 and FE2 and the formyl group that connects the thienyl ring to the furylethyle ne moiety in FE3. Among the furylethylenes tested, only FE1 was found to react effectively with beta-mercaptoethanol (beta ME) and glycine ( GLY) as model substances containing nucleophilic groups, and also exhi bit an inhibitory interaction with the (Na/K)-ATPase. A suppression of the reactivity of the formyl group due to the replacement of the fury l ring with the more aromatic thienyl ring in FE3 did not induce any s ignificant change in the reactivity of the compound with the model sub stances or with (Na/K)-ATPase. On the other hand, replacement of the N O2 group on the furylethylene moiety (in FE1) by the less electron-att racting phenylsulfonyl group (in FE2 and FE3) yielded a considerable s uppression of the inhibitory effect on (Na/K)-ATPase. Moreover, in com parison to FE1, FE2 and FE3 were found to react less potently with the model nucleophilic substances. The results indicated that the conjuga ted triene moiety on the furylethylene part of the molecule of FE1 may be made responsible for the inhibitory interaction with the nucleophi lic aminoacid residue on the (Na/K)-ATPase-molecule. FE1 interfered co mpetitively with the (Na/K)-ATPase activation by increasing amounts of potassium. This was manifested by a significant increase in the appar ent K-0.5(App) value and a decrease in the apparent cooperativity cons tant, n(App), for potassium ions, but had no influence on the apparent V-max(App) value for potassium. With respect to the activation of the enzyme with sodium ions and ATP, only FE1 decreased the V-max(App) va lues while having no considerable influence on the other kinetic varia bles. It was concluded that FE1 inhibits the (Na/K)-ATPase by selectiv e interaction with some essential nucleophilic (probably SH and/or NH2 ) aminoacid residues located in, or closed to the potassium binding si te of the enzyme molecule.