Brain (Na+ + K+)-activated adenosine triphosphatase activity and neurotransmitter uptake in alcohol-dependent rats

Roach, Mary K.; Khan, Mohammad Moshahid; Coffman, Rebecca; Pennington, Willie; Davis, D.

doi:10.1016/0006-8993(73)90099-1

Cited by 71 publications

(8 citation statements)

References 15 publications

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“…The increase in the level of brain (Na + K)-ATPase without change in M$+-ATPase confirms previous work [38,39]. As discussed by Israel et al [38], since ethanol inhibits (Na + K)-ATPase activity in vitro, and may do so in vivo, an increased activity of the ATPase may compensate for impaired neuronal function in rats on a high and prolonged ethanol intake.…”

Section: Discussionsupporting

confidence: 90%

The Influence of Prolonged Ethanol Intake on the Levels and Turnover of Alcohol and Aldehyde Dehydrogenases and of Brain (Na + K)‐ATPase of Rats

Guerri

Wallace

Grisolı́a

1978

European Journal of Biochemistry

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Levels of liver alcohol dehydrogenase, liver mitochondrial aldehyde dehydrogenase and brain (Na + K)-stimulated ATPase were determined in control rats and in rats fed an ethanol liquid diet for 7 weeks. The alcohol dehydrogenase level did not change with the diet; however, the levels of mitochondrial aldehyde dehydrogenase and of the (Na + K)-ATPase were increased 2.5-fold and 2-fold respectively. Also, the levels of these enzymes from brain and liver fractions of rats given a 20 % ethanol solution as the sole drinking fluid were determined at intervals from 4 to 18 weeks. A progressive increase was found in the level of aldehyde dehydrogenase and of ATPase.To ascertain whether synthesis or degradation of these enzymes were responsible for the marked increase in activity the turnover of several liver fractions and of the indicated enzymes were measured by the dual-labelled isotope technique. Long-term ethanol administration did not affect the rate of turnover of the liver cell fractions except for the mitochondrial fraction. This fraction showed a marked decrease in the rate of degradation. The degradation constant of the liver alcohol dehydrogenase did not change; however, the rate of degradation of liver mitochondrial aldehyde dehydrogenase (10w-K~) and of brain (Na + K)-ATPase was decreased.It has been established that about 90 % of ingested ethanol is metabolized in the liver [l] and that the rate of ethanol metabolism is markedly increased in animals, including man, after chronic ethanol consumption [2 -41. Alcohol dehydrogenase located mainly in hepatic parenchymal cells is primarily responsible for the conversion of ethanol to acetaldehyde [5]. It has been proposed that an increase in ethanol utilization would result .in a concomitant increase in alcohol dehydrogenase levels ; although this suggestion remained controversial for a number of years [6] it appears now that the increase in the rate of ethanol metabolism arising from chronic usage can occur without changes in alcohol dehydrogenase activity [2,7,8].It is now generally accepted that more than 90% of the acetaldehyde formed from ethanol is oxidized in the liver. Several aldehyde dehydrogenases characterized by their differential affinities for acetaldehyde

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Section: Discussionsupporting

confidence: 90%

The Influence of Prolonged Ethanol Intake on the Levels and Turnover of Alcohol and Aldehyde Dehydrogenases and of Brain (Na + K)‐ATPase of Rats

Guerri

Wallace

Grisolı́a

1978

European Journal of Biochemistry

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“…More recent ly, a close correlation between brain Na-KATPase activity and the development of eth anol tolerance was again demonstrated [42]. Similar results have been reported by other laboratories using alternative means of etha nol administration (e.g., chronic ethanol in halation for 7 days [43]; liquid diet adminis tration for 2-7 weeks [44,45]; oral intuba tion for 7 days [46]). Other reports which, on the surface, seem contradictory are also available.…”

Section: Ethanol and Na-k-atpase Activity Insupporting

confidence: 75%

Effects of Ethanol on the Activity of Brain Enzymes

Tabakoff

Hoffman

Liljequist³

1987

Enzyme

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Ethanol alters, in a selective manner, the activity of several membrane-bound enzymes in the central nervous system (CNS) which are important for neuronal transmission of information. Ethanol inhibits Na^+/K^+-transporting ATPase activity, while adenylate cyclase (AC) activity is stimulated by ethanol added in vitro. Ethanol’s effects on AC activity are mediated primarily via effects on proteins that regulate AC activity. Ethanol has selective effects on monoamine oxidase activity, in that the B form of the enzyme is more sensitive to inhibition by ethanol added in vitro. The selective effects of ethanol on different membranebound CNS enzymes may result from differing membrane lipid microenvironments of the enzymes, or from differences in the enzyme proteins per se.

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“…The question that has occupied us and many other investigators is whether study of animals under laboratory control might shed some light on this self-destructive behavior. To date no complete counterpart of human alcoholism-life-threatening toxicity from voluntary intake-has been found in animals, although many partial models of the disease are available (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16).…”

mentioning

confidence: 99%

Toward an analogue of alcoholism in mice: scale factors in the model.

Dole¹,

Gentry²

1984

Proc. Natl. Acad. Sci. U.S.A.

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Mice of the C57BL strain, given continuous access to 10% alcohol and plain water, with unlimited food and no stress, frequently drink enough alcohol to produce intoxicating levels in the blood. Nevertheless, this behavior does not appear to replicate the essential features of human alcoholism since the drinking lacks serious toxic effects and the intoxication occurs only as transient episodes in association with homeostatic consumption of fluid and food. It is suggested that continuous monitoring of intake and estimation of the concentration of alcohol in blood, which are now technically feasible, will permit distinction between alcoholic-type drinking and a simple licking for the flavor of alcohol in beverage concentration.Consumption of alcohol by human alcoholics is both voluntary and excessive. Despite suffering from gastritis, loss of social status from repeated episodes of intoxication, and progressive deterioration of health, a severe alcoholic is likely to drink compulsively until death. The question that has occupied us and many other investigators is whether study of animals under laboratory control might shed some light on this self-destructive behavior. To date no complete counterpart of human alcoholism-life-threatening toxicity from voluntary intake-has been found in animals, although many partial models of the disease are available (1-16).The hope of understanding the basic cause of alcoholism through study of animals could be illusory since human motivation involves cognitive stresses that are not known to occur in animals. If such stress is the essential determinant of alcoholism, then animal studies will always be peripheral to the main problem, limited to analyzing the consequences rather than the causes of excessive drinking. On the other hand, this view may be too pessimistic. Some animals, such as the mice used in the present study, choose to drink solutions of alcohol in preference to plain water. Animals under constraints that force them to greater intakes of alcohol than they would exhibit if an unlimited supply of water and food were available show some of the toxic effects seen in alcoholics, but what is not known is whether these animals drink alcohol for its pharmacological effect or as a source of calories (17).The toxic effects of alcohol depend on its concentration in vulnerable tissues and on accumulation of toxic metabolites. These variables, in turn, involve a number of scale factors, such as rates of ingestion, distribution, and elimination. The differences in scale between species are substantial, and no single scale factor adequately describes the differences. The mass of a mouse is only 0.0004 times that of a man. Although the water content per unit body weight (and therefore the volume of distribution for alcohol) is about the same in the two species, the metabolism of alcohol per unit weight differs by a factor of about 5 and the rate of total oxidative metabolism per unit weight differs by a factor of about 15. Thus, the ingestion of a given quantity of alcohol p...

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Brain (Na+ + K+)-activated adenosine triphosphatase activity and neurotransmitter uptake in alcohol-dependent rats

Cited by 71 publications

References 15 publications

The Influence of Prolonged Ethanol Intake on the Levels and Turnover of Alcohol and Aldehyde Dehydrogenases and of Brain (Na + K)‐ATPase of Rats

The Influence of Prolonged Ethanol Intake on the Levels and Turnover of Alcohol and Aldehyde Dehydrogenases and of Brain (Na + K)‐ATPase of Rats

Effects of Ethanol on the Activity of Brain Enzymes

Toward an analogue of alcoholism in mice: scale factors in the model.

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