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.