Interaction of catecholamines and ethanol on the kinetics of rat brain (Na+ + K+)-ATPase.
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 Vmax or Km for K+, Na+, Mg2+ 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 Mg2+ : ATP ratios. CA alone decreased the Km slightly for K+ and by about 50% for ATP, increased it for Mg2+ 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 Mg2+, 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 E2P for to the inwardly facing Na+-binding E1P form.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002395:Catecholamines / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D002395:Catecholamines; D000431:Ethanol; D000255:Adenosine Triphosphate; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D008274:Magnesium; D011188:Potassium; D004298:Dopamine; D009638:Norepinephrine