南天竹宁对突触体膜K⁺-对硝基苯磷酸酶活性的体外剂量依赖性反向作用。

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

作者信息

Ribeiro R A, Rodríguez de Lores Arnaiz G

机构信息

Instituto de Biología Celular y Neurociencias Prof. Eduardo De Robertis, PROBICENE-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay, Argentina.

出版信息

Phytomedicine. 2001 Mar;8(2):107-11. doi: 10.1078/0944-7113-00013.

DOI:10.1078/0944-7113-00013

PMID:11315751

Abstract

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.

摘要

以对硝基苯磷酸酯（p-NPP）为底物，评估了阿朴啡生物碱南天竹宁对ATPase K⁺依赖性去磷酸化的影响。基础K⁺-p-NPPase活性在3×10⁻⁴ M时显著增加，在3×10⁻⁶ M、3×10⁻⁵ M时保持不变，但在7.5×10⁻⁴ M和1×10⁻³ M南天竹宁时降低，而Mg²⁺-p-NPPase活性未改变。动力学研究表明，南天竹宁对K⁺-p-NPPase的抑制作用对KCl具有竞争性，但对底物p-NPP无竞争性，而南天竹宁对K⁺-p-NPPase的刺激作用对KCl无竞争性，但对p-NPP具有竞争性。这些数据表明，在p-NPPase中可能存在两个南天竹宁的受体位点，一个引起对K⁺依赖性p-NPP水解的刺激，另一个引起抑制。考虑到南天竹宁对癫痫发作的双相作用以及ATPase活性降低与癫痫发作发展之间的相关性，低剂量南天竹宁观察到的生物碱抗惊厥作用归因于磷酸酶活性的刺激，而高生物碱剂量时的惊厥作用似乎与Na⁺,K⁺-ATPase抑制有关。