Inhibition of (Na+, K+)-ATPase by fluoride: evidence for a membrane adaptation to ethanol.
Fluoride ions inhibit several membrane enzymes in a manner that is dependent on membrane fluidity. Inhibition of (Na+, K+)-ATPase by fluoride ions may be a model for membrane effects on (Na+, K+)-ATPase. Therefore, we have examined properties of fluoride inhibition relative to interactions with ethanol and to ligands that alter sensitivity of (Na+, K+)-ATPase to ethanol. Fluoride ion reduced the K0.5 and Hill coefficient for K+ activation of p-nitrophenylphosphatase. Ethanol decreased the Hill coefficient and apparent affinity for inhibition of phosphatase activity by fluoride ion while dimethylsulfoxide had the opposite effects. Chronic ethanol treatment in vivo, which produced behavioral tolerance, had effects on fluoride inhibition opposite to those of ethanol in vitro. Inhibition by fluoride therefore may provide a useful marker for physiologic or pharmacologic conditions that alter regulation of (Na+, K+)-ATPase by membrane properties.
Swann
A C
AC
Department of Psychiatry and Behavioral Sciences, University of Texas Medical School, Houston 77225.
D000818:Animals; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004361:Drug Tolerance; D000431:Ethanol / Q000494:pharmacology*; D005459:Fluorides / Q000494:pharmacology*; D008560:Membrane Fluidity / Q000187:drug effects*; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D000431:Ethanol; D010744:Phosphoric Monoester Hydrolases; D000254:Sodium-Potassium-Exchanging ATPase; D005459:Fluorides; D011188:Potassium; D004121:Dimethyl Sulfoxide