Brain Na+,K+-ATPase: alteration of ligand affinities and conformation by chronic ethanol and noradrenergic stimulation in vivo.
These experiments examined effects of chronic ethanol, repeated noradrenergic stimulation or inhibition, and ethanol combined with the noradrenergic treatments on regulation of Na+,K+-ATPase. Chronic treatment with ethanol reduced the sensitivity of K+-p-nitrophenyl-phosphatase to ethanol, increased affinity for K+, reduced the sensitivity of K+ affinity to ATP or ethanol, and reduced delta H and delta S for K+ activation and for the E1-E2 transition. These effects were all opposite to those of ethanol added in vitro. Treatment with yohimbine had the opposite effects on ethanol sensitivity, K+ affinity, K+ interactions with ethanol and ATP, and thermodynamic parameters for cation activation or conformational change. These effects were similar to those of norepinephrine in vitro. The effects of yohimbine treatment were eliminated or reduced in rats also treated with ethanol. Depletion of norepinephrine had effects opposite to those of yohimbine. These data are consistent with a reduction in membrane fluidity, at least in the vicinity of Na+,K+-ATPase, during ethanol tolerance. Exposure to norepinephrine, in vitro or in vivo, had effects on Na+,K+-ATPase that were similar to those of increased membrane fluidity.
D009597:4-Nitrophenylphosphatase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011487:Protein Conformation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013816:Thermodynamics; D015016:Yohimbine / Q000494:pharmacology
D015016:Yohimbine; D000431:Ethanol; D000255:Adenosine Triphosphate; D012964:Sodium; D009597:4-Nitrophenylphosphatase; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D009638:Norepinephrine