Veratrine-induced decrease of (Na+ + K+)-adenosine triphosphatase activity in rat brain slices

T Matsuda and H Iwata

Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University, Japan.

The effect of membrane excitability on (Na+ + K+)-adenosine triphosphatase (ATPase) was studied in rat brain slices. The treatment of the brain cortical slices with veratrine for more than 10 min caused a significant decrease of the (Na+ + K+)-ATPase activity. The similar inhibition of the enzyme by veratrine was observed in the hippocampus and hypothalamus, and the veratrine treatment did not affect the sensitivity of the cortical enzyme for ouabain inhibition. These findings suggest that two isozymes of (Na+ + K+)-ATPase are equally inhibited by the treatment. Veratrine inhibited the partial reactions such as Na+-dependent phosphorylation and K+-stimulated phosphatase as well as the specific binding of [3H]ouabain. Agents which increase intracellular Na+ concentration also inhibited the enzyme activity. The effects of veratrine were blocked by Na+-free medium or tetrodotoxin. Low Na+ medium decreased the enzyme activity, and the effect was blocked by amiloride or Ca++-free medium, indicating the involvement of Na+/Ca++ exchange in the inhibition. The decreased activity induced by low Na+ or high K+ medium was restored to the normal level by the subsequent incubation in normal medium. The inhibitory effect of veratrine was dependent on external Ca++, and was blocked by addition of W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide]. A23187 also decreased (Na+ + K+)-ATPase activity in the slices. High Mg++ medium blocked the effect of veratrine but not that of monensin which was not dependent on external Ca++.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 248, Issue 2, pp. 729-735, 02/01/1989
Copyright © 1989 by American Society for Pharmacology and Experimental Therapeutics