MASTOPARAN INHIBITS RAT RENAL NAK-ATPASE ACTIVITY

Rat renal NAK-ATPase was inhibited by mastoparan in a dose dependent fashion. This inhibition reached completion within 30 seconds. Due to mastoparan's rapid effects on NAK-ATPase activity, this inhibition does not appear to involve either a decrease in the rate of synthesis or an increase in their degradation of NAK-ATPase since these processes require a latency period of at least several minutes. In addition, the phosphoenzyme intermediate formed in the presence of mastoparan was greater than that formed in its absence further indicating that inhibition of NAK-ATPase by mastoparan is not due to a decrease in the number of NAK-ATPase. A possible mechanism for the inhibition is that mastoparan stabilizes the phosphoenzyme intermediate and reduces the Vmax of the enzyme by decreasing the rate of turnover of existing enzyme sites. Neomycin, an inhibitor of inositol phospholipid metabolism, was also found to attenuate the inhibition of Na,K-ATPase by mastoparan, suggesting that the mechanism of this inhibition may involve degradation of the phosphatidylinositol "pool". © 1991.