Ethanol modulates calmodulin-dependent Ca(2+)-activated ATPase in synaptic plasma membranes.
The effects of ethanol in vitro on calmodulin-dependent Ca(2+)-activated ATPase (CaM-Ca(2+)-ATPase) activity were studied in synaptic plasma membranes (SPM) prepared from the brain of normal and chronically ethanol-treated rats. In SPM from normal animals, ethanol at 50-200 mM inhibited the Ca(2+)-ATPase activity. Lineweaver-Burk analysis indicates that the inhibition was the result of a decreased affinity of the enzyme for calmodulin, whereas the maximum activity of the enzyme was not changed. Arrhenius analysis indicates that the enzyme activity was influenced by lipid transition of the membranes, and ethanol in vitro resulted in a shift of the transition temperature toward a lower value. From animals receiving chronic ethanol treatment (3 weeks), the SPM were resistant to the inhibitory effect of ethanol on the enzyme activity. The resistance to ethanol inhibition was correlated with a higher enzyme affinity for calmodulin and a higher transition temperature, as compared with normal SPM. Since the calmodulin-dependent Ca(2+)-ATPase in synaptic plasma membranes is believed to be the Ca2+ pump controlling free Ca2+ levels in synaptic terminals, its inhibition by ethanol could therefore lead to altered synaptic activity.
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Department of Pharmacology and Molecular Biology, Chicago Medical School, Illinois 60064.
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D000437:Alcoholism / Q000201:enzymology*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D000252:Calcium-Transporting ATPases / Q000187:drug effects / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013570:Synaptic Membranes / Q000201:enzymology*; D013574:Synaptosomes / Q000201:enzymology; D014268:Trifluoperazine / Q000494:pharmacology
D007093:Imidazoles; D014268:Trifluoperazine; D000431:Ethanol; C031938:calmidazolium; D010042:Ouabain; D000252:Calcium-Transporting ATPases