Abstract
The effects of 1 uM concentrations of arachidonic acid hydroperoxide (HPETES) products of 5-, 12- and 15-lipoxygenase on Na+, K+-ATPase activity were investigated in synaptosomal membrane preparations from rat cerebral cortex. 5-HPETE inhibited Na+, K+-ATPase activity by up to 67 %. In contrast, 12-HPETE and 15-HPETE did not inhibit Na+, K+-ATPase activity. In addition, neither 5-HETE or LTA4inhibited Na+, K+-ATPase activity. Dose-response studies indicated that 5-HPETE was a potent (IC25= 10−8M) inhibitor of Na+, K+-ATPase activity. These findings indicate that 5-HPETE inhibits Na+, K+-ATPase activity by a mechanism that is dependent on the hydroperoxide position and independent of further metabolism by 5-lipoxygenase. It is proposed that 5-HPETE production by 5-lipoxygenase and subsequent inhibition of neuronal Na+, K+-ATPase activity may be a mechansim for modulating synaptic transmission.
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