Interaction of catecholamines and ethanol on the kinetics of rat brain (Na + + K +)-ATPase

Abstract

The effects of catecholamines (CA) and ethanol (EtOH), singly and in combination, on the kinetics of rat brain (Na + + K +)-ATPase were studied. Addition of 0.05 M EtOH alone did not change V max or K m for K +, Na +, Mg 2+ and ATP. Addition of 0.1 mM dopamine (DA) or noradrenaline (NA) alone stimulated the enzyme activity in presence of vanadium-containing ATP as substrate, but not with vanadium-free ATP except in the presence of high Mg 2+ : ATP ratios. CA alone decreased the K m slightly for K + and by about 50% for ATP, increased it for Mg 2+ and did not change it for Na +. However, the combination of DA or NA + EtOH produced a marked inhibition which was competitive for K +, and uncompetitive or mixed for Mg 2+, Na + and ATP. The inhibitory effect of NA + EtOH was abolished in 20 mM K +. These findings suggest that NA sensitizes the enzyme to EtOH inhibition at physiological K + concentrations, by conformational change away from the outwardly facing K +-binding E 2P form to the inwardly facing Na +-binding E 1P form.