Acute and chronic catecholamine-ethanol interactions on rat brain (Na+ + K+)-ATPase.
Noradrenaline (N) sensitizes rat brain (Na+ + K+)-ATPase to inhibition by low concentrations of ethanol (E). Only 1-N and not d-N was effective. The sensitization is also produced by other alpha-adrenergic agonists (adrenaline, phenylephrine), but not by isoproterenol, and is prevented by phentolamine but not by propranolol. The sensitization is greater with partially purified enzyme than with crude homogenates. N + E, like much higher concentrations of E alone, produced competitive inhibition with respect to K+ but uncompetitive or mixed inhibition with respect to Na+, Mg++ and ATP, and a reduced "physiological efficiency" of ATP utilization. All these changes were abolished by increasing K+ to 20 mM. After 3-week E treatment, with or without withdrawal, the N + E interaction was markedly reduced, though basal ATPase activity was increased only after withdrawal. Temperature-dependence studies (Arrhenius plots) indicated that sensitization occurs by alteration of activation energy only above the transition temperature. These findings suggest that alpha-agonists fluidize membrane lipids and thus facilitate conformational change of the enzyme by E, resulting in inhibition.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002395:Catecholamines / Q000494:pharmacology*; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000201:enzymology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013574:Synaptosomes / Q000201:enzymology
D002395:Catecholamines; D000431:Ethanol; D000254:Sodium-Potassium-Exchanging ATPase; D009638:Norepinephrine