CELL BIOCHEMISTRY AND FUNCTION VOL.
9: 215-222 (1991)
Effect of Chronic Ethanol Consumption on Postnatal Development of Renal (Na + K)-ATPase in the Rat RAMON RODRIGO, LEONCIO VERGARA AND ERNEST0 OBERHAUSER Dvpartment of Experimental Medicine, Faculty of Medicine, University of Chile, Santiago, Chile
Renal (Na + K)-ATPase was studied to ascertain whether it follows the pattern of adaptation of membrane-bound enzymes that are inhibited by acute ethanol exposure and develop greater activity after chronic ethanol treatment. A colony of rats was given 20 per cent (v/v) ethanol as sole drinking solution throughout gestation, lactation and following weaning. (Na + K)-ATPase and ouabain-insensitive Ca2+-ATPase activities were determined; regional distribution of these enzymes was assessed in renal cortex and outer medulla. Control rats drank tap water. (Na + K)-ATPase in whole homogenate of kidney increased with age in controls and ethanol-fed rats, but the latter showed higher values at every age studied. Between 15 and 60 days of age, the control group showed 2-fold increases in cortex and 5-fold in outer medulla, whereas ethanol-fed rats reached a 3-fold increase in the enzyme activity in both renal regions. Ca2+-ATPase showed the same time course in developing kidney of both groups. Chronic ethanol treatment of adult rats resulted in an increase of (Na + K)-ATPase activity in cortex and outer medulla, but no change in other ATPases. Since an earlier maturational development of renal (Na + K)-ATPase was displayed by ethanol-fed rats, underlying mechanisms that may account for these results are discussed. K E Y WORDS
Ethanol; (Na
+ K)-ATPase; kidney; postnatal
development.
sorption of sodium by the kidney,"-" may explain isoosmotjc overhydration seen after ethanol adThe biological effects of ethanol may be partially ministration in humans (without serious liver related to its effects on lipid membranes.' Acutely, damage),13 dogs14 and rats.ls ethanol causes a disordering (fluidizing) effect on The immediate postnatal state is characterized lipid bilayers whereas chronic administration in- by a limited ability to excrete sodium associated duces membrane tolerance (adaptations that reduce with a positive sodium b a 1 a n ~ e . lRenal ~ (Na the sensitivity of the membranes to the disordering K)-ATPase activity in this state is OW.'^'^^ The effect).' (Na K)-ATPase, like other membrane- activity of renal (Na + K)-ATPase increases with - ~ from the low of the immediate postnatal period bound enzymes, is inhibited by ethanol in ~ i t r o ~ age but its specific activity may increase after chronic to adult levels in both rats and rabbit^.'^.'^ The ethanol administration in uiua6 In the brain, (Na maturation of the (Na K)-ATPase activity has K)-ATPase activity has been reported to increase the same time course in the proximal tubule as the after long-term ethanol administration in maturation of the capacity to reabsorb water in the Because the (Na + K)-ATPase content of the kid- rat" and solute in the rabbit.2o ney is very high it is reasonable to postulate that It has been recently suggested that membrane the activity of this enzyme in renal tissue might adaptation to the chronic effect of ethanol in viuo is increase after the chronic administration of eth- the expression of alterations in (Na + K)-ATPase anol. However, there is no data available in this activity.2' It is therefore reasonable to postulate regard. An increase in the activity of (Na + that kidney (Na + K)-ATPase may respond to K)-ATPase, that plays a central role in the reab- ethanol administration in both adult and growing animals, although the latter are perhaps more sensitive. The aim of the present experiments was to Addressee for correspondence: Dr Ram6n Rodrigo, Department ascertain the effects of chronic ethanol administraof Experimental Medicine, Faculty of Medicine, University of Chile. Casilla 70058, Santiago 7, Chile. tion on renal (Na K)-ATPase during postnatal INTRODUCTION
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0263 6484/91/030215-08 $05.00
9: 215-222 (1991)
Effect of Chronic Ethanol Consumption on Postnatal Development of Renal (Na + K)-ATPase in the Rat RAMON RODRIGO, LEONCIO VERGARA AND ERNEST0 OBERHAUSER Dvpartment of Experimental Medicine, Faculty of Medicine, University of Chile, Santiago, Chile
Renal (Na + K)-ATPase was studied to ascertain whether it follows the pattern of adaptation of membrane-bound enzymes that are inhibited by acute ethanol exposure and develop greater activity after chronic ethanol treatment. A colony of rats was given 20 per cent (v/v) ethanol as sole drinking solution throughout gestation, lactation and following weaning. (Na + K)-ATPase and ouabain-insensitive Ca2+-ATPase activities were determined; regional distribution of these enzymes was assessed in renal cortex and outer medulla. Control rats drank tap water. (Na + K)-ATPase in whole homogenate of kidney increased with age in controls and ethanol-fed rats, but the latter showed higher values at every age studied. Between 15 and 60 days of age, the control group showed 2-fold increases in cortex and 5-fold in outer medulla, whereas ethanol-fed rats reached a 3-fold increase in the enzyme activity in both renal regions. Ca2+-ATPase showed the same time course in developing kidney of both groups. Chronic ethanol treatment of adult rats resulted in an increase of (Na + K)-ATPase activity in cortex and outer medulla, but no change in other ATPases. Since an earlier maturational development of renal (Na + K)-ATPase was displayed by ethanol-fed rats, underlying mechanisms that may account for these results are discussed. K E Y WORDS
Ethanol; (Na
+ K)-ATPase; kidney; postnatal
development.
sorption of sodium by the kidney,"-" may explain isoosmotjc overhydration seen after ethanol adThe biological effects of ethanol may be partially ministration in humans (without serious liver related to its effects on lipid membranes.' Acutely, damage),13 dogs14 and rats.ls ethanol causes a disordering (fluidizing) effect on The immediate postnatal state is characterized lipid bilayers whereas chronic administration in- by a limited ability to excrete sodium associated duces membrane tolerance (adaptations that reduce with a positive sodium b a 1 a n ~ e . lRenal ~ (Na the sensitivity of the membranes to the disordering K)-ATPase activity in this state is OW.'^'^^ The effect).' (Na K)-ATPase, like other membrane- activity of renal (Na + K)-ATPase increases with - ~ from the low of the immediate postnatal period bound enzymes, is inhibited by ethanol in ~ i t r o ~ age but its specific activity may increase after chronic to adult levels in both rats and rabbit^.'^.'^ The ethanol administration in uiua6 In the brain, (Na maturation of the (Na K)-ATPase activity has K)-ATPase activity has been reported to increase the same time course in the proximal tubule as the after long-term ethanol administration in maturation of the capacity to reabsorb water in the Because the (Na + K)-ATPase content of the kid- rat" and solute in the rabbit.2o ney is very high it is reasonable to postulate that It has been recently suggested that membrane the activity of this enzyme in renal tissue might adaptation to the chronic effect of ethanol in viuo is increase after the chronic administration of eth- the expression of alterations in (Na + K)-ATPase anol. However, there is no data available in this activity.2' It is therefore reasonable to postulate regard. An increase in the activity of (Na + that kidney (Na + K)-ATPase may respond to K)-ATPase, that plays a central role in the reab- ethanol administration in both adult and growing animals, although the latter are perhaps more sensitive. The aim of the present experiments was to Addressee for correspondence: Dr Ram6n Rodrigo, Department ascertain the effects of chronic ethanol administraof Experimental Medicine, Faculty of Medicine, University of Chile. Casilla 70058, Santiago 7, Chile. tion on renal (Na K)-ATPase during postnatal INTRODUCTION
+
+
+
+
+
0263 6484/91/030215-08 $05.00
