Abstract
Na+, K+-ATPase activity of brain microsomal fractions prepared from rats treated with the cholesterol biosynthesis inhibitor AY 9944 was found to be markedly increased when compared with nontreated control fractions. Both control and AY 9944-treated preparations increase their Na+, K+-ATPase activity with increasing temperatures; such increments were higher in the microsomal fractions prepared from the AY 9944-treated rats than those from the untreated controls. The apparent Km calculated for Na+, K+ and Mg2+, as well as the optimal ratio Mg2+/ATP of the Na+, K+-ATPase from both microsomal fractions, were found to be the same in each case. The binding of [3H]-ouabain as a function of time, as well as a function of the incubation temperature, was also the same in both preparations. If it is considered that treatment with AY 9944 results in the partial substitution of cholesterol by 7-dehydrocholesterol without modifying any other constituent in the microsomal membranes, the observed increment in the Na+, K+-ATPase activity could be interpreted as the result of an increased membrane "fluidity" and shows that Na+, K+-ATPase activity is dependent upon the environmental sterol composition.
ACKNOWLEDGMENTS The authors are grateful for the stimulating criticism of Dr. Joseph Hoffmann, the excellent technical assistance of Mrs. T. Proverbio and the efficient secretarial help of Mrs. Consuelo Vargas. The drug AY 9944 was kindly supplied by Dr. D. Dvornik from Ayerst Laboratories, Montreal.
- Copyright © 1978 by Academic Press, Inc.
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