In vitro dose dependent inverse effect of nantenine on synaptosomal membrane K+-p-NPPase activity.

The effect of nantenine, an aporphine alkaloid, on ATPase K+-dependent dephosphorylation was evaluated using p-nitrophenylphosphate (p-NPP) as substrate. Basal K+-p-NPPase activity was significantly increased with 3 x 10(-4) M, remained unchanged with 3 x 10(-6) M, 3 x 10(-5) M but was reduced with 7.5 x 10(-4) M and 1 x 10(-3) M nantenine, whereas Mg2+-p-NPPase activity was not modified. Kinetic studies showed that K+-p-NPPase inhibition by nantenine is competitive to KCl but non-competitive to substrate p-NPP, whereas K+-p-NPPase stimulation by nantenine is non-competitive to KCl but competitive to p-NPP. These data suggest that there may be two acceptor sites for nantenine in p-NPPase, one eliciting stimulation and the other inhibition of K+-dependent p-NPP hydrolysis. Considering the biphasic action of nantenine on seizures and the correlation between decreased ATPase activity and seizure development, alkaloid anticonvulsant effect observed at low nantenine doses is attributable to the stimulation of phosphatase activity whereas the convulsant effect at high alkaloid doses seems related to Na+, K+-ATPase inhibition.