The effects of ethanol on the activities of five membrane bound enzymes were determined using a crude membrane preparation obtained from cortex of long-sleep (LS) and short-sleep (SS) mice. These two mouse lines were selectively bred for differences in duration of ethanol-induced sleep time. The enzymes studied were two forms of NaK-ATPase, Mg-ATPase, 5'nucleotidase, and acetylcholinesterase. Arrhenius plots of the ethanol-temperature-enzyme activity studies indicate specificity in ethanol's actions. NaK-ATPase activity consists of two enzymes which were distinguished by sensitivity to ouabain. The Arrhenius plot of the high ouabain sensitivity enzyme (low Ki) exhibited a transition temperature which was reduced twice as much by ethanol in LS membranes as in SS membranes. Ethanol did not affect the transition temperature of the high Ki NaK-ATPase but the control (no ethanol) transition temperature was 2.7 degrees higher in SS membranes. Arrhenius plots of Mg-ATPase activity did not exhibit a transition temperature and ethanol did not alter enzyme activity. Ethanol did not alter the transition temperatures of 5'nucleotidase or acetylcholinesterase but the control transition temperature for acetylcholinesterase was 2.3 degrees higher in SS membranes. These results indicate specificity in ethanol's actions on membranes and that inhibition of the lipid-enzyme interactions for the low Ki NaK-ATPase is correlated with the difference in sensitivity to ethanol seen between the LS and SS mice.

5'-Nucleotidase↗

PubMedDate not supplied

Ethanol-nicotine interactions in long-sleep and short-sleep mice.

The possibility that common genetic factors regulate initial sensitivities to ethanol and nicotine as well as the development of cross-tolerance between these agents was explored using the long-sleep (LS) and short-sleep (SS) mice. The LS mice proved to be more sensitive to an acute challenge with nicotine than were the SS mice. Segregation analysis (F1, F2, backcross) indicated that ethanol sensitivity and nicotine sensitivity segregate together. Acute pretreatment with nicotine did not significantly affect sensitivity to ethanol, but ethanol pretreatment altered nicotine responsiveness. The LS mice develop more tolerance to nicotine and ethanol than do the SS and they also develop more cross-tolerance. These genetically determined differences in initial sensitivities, and tolerance and cross-tolerance development are not readily explained by differences in brain nicotinic receptor numbers.

Animals↗

PubMedDate not supplied

Genotype regulates the development of tolerance to ethanol and cross-tolerance to nicotine.

The long-sleep (LS) and short-sleep (SS) mouse lines were selectively bred for differential sensitivity to the anesthetic actions of ethanol, but they also differ in sensitivity to nicotine. A recent study suggested that the LS mice develop more tolerance to ethanol and cross-tolerance to nicotine than do the SS following chronic ethanol treatment. The studies reported here expand on these previous studies by assessing potential tolerance to ethanol and cross-tolerance to nicotine using additional behavioral and physiological measures. In addition, the effects of chronic ethanol treatment on ethanol and nicotine metabolism were measured. The LS mice developed tolerance to ethanol as measured by effects on open-field activity, body temperature, and sleep time, whereas the SS mice did not develop consistent tolerance to ethanol's effects on any of these measures. Cross-tolerance to nicotine's effects on open-field activity and body temperature developed, but only in the LS mice. The ethanol tolerance is likely due to changes in CNS sensitivity to ethanol, but altered elimination of nicotine may explain much of the cross-tolerance to nicotine seen in chronic ethanol-treated LS mice.

Absorption↗

PubMedDate not supplied

Successful restoration of renal allograft function with urokinase thrombolysis in the setting of phlegmasia cerulea dolens.

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Aged↗

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Use of a curved needle for true lumen re-entry during subintimal iliac artery revascularization.

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Angiography↗

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Brain NaK-ATPases in mice differentially sensitive to alcohols.

The isozymes of NaK-ATPase were studied in the particulate fraction of homogenates prepared from cortex of LS and SS mice, two lines of mice that have been selectively bred for differential response to ethanol. In addition to a ouabain-insensitive Mg-ATPase, ouabain dose-response curves have suggested the presence, in brain, of two NaK-ATPase activities with different sensitivities to ouabain. These are designated low Ki (4 X 10(-7) M) and high Ki (2 X 10(-4) M). Ethanol differentially inhibited the ATPases: The ouabain-insensitive activity was less sensitive to ethanol inhibition than were the two ouabain-inhibitable activities. The low Ki (brain specific) NaK-ATPase was more sensitive than was the high Ki activity. However, ethanol inhibited all three components of the ATPase activity in an identical fashion in the two mouse lines. The low Ki activity was also more labile to thermal and p-hydroxymercurobenzoate denaturation than was the high Ki activity. These measures did not differ between the LS and SS lines. SDS-polyacrylamide electrophoresis of particulate fraction of cortical homogenates obtained from LS and SS mice revealed the presence of two protein bands with similar 32P labeling in both lines. Given that electrophoretic pattern and heat or p-hydroxymercurobenzoate inhibition were identical, it seems unlikely that differences in ATPase activity, or inhibition by ethanol, are responsible for the different response of LS and SS mice to ethanol.

Animals↗

PubMedDate not supplied

Dose and route of administration alter the relative elimination of ethanol by long-sleep and short-sleep mice.

The elimination of ethanol following the intravenous and intraperitoneal administration of five ethanol doses was measured in two mouse lines, the long-sleep (LS) and short-sleep (SS), that differ markedly in central nervous system sensitivity to ethanol. Both dose and route of administration affected the relative ethanol elimination in these two mouse lines. When the ethanol was given i.v., a steady increase in elimination rate was seen in the SS mice as the dose was increased. In the LS mice, consistent changes in rate with dose were not seen. At the lower doses tested, the LS eliminated ethanol more rapidly than did the SS but at higher doses the mouse lines did not differ. When the ethanol was given i.p., increases in rate with dose were not seen. Rather, the SS elimination rate remained constant as the dose was increased, whereas in the LS a decrease in rate was observed. As a consequence, the SS eliminated ethanol more rapidly than did the LS at higher doses. A potential explanation for these results is that ethanol elimination, following the administration of large doses, is affected by both enzymological factors and central nervous system sensitivity to ethanol. The central nervous system factors may be mediated via ethanol-induced hypothermia.

Alcohol Oxidoreductases↗