title: Na(+)/K(+)-ATPase inhibition upregulates NMDA-evoked currents in rat hippocampal CA1 pyramidal neurons.
abstract: Na(+)/K(+)-ATPase and N-methyl-D-aspartate (NMDA) receptor in hippocampus play very important roles in the regulation of learning and memory. Here, we showed that dihydroouabain (DHO, 10(-5)-10(-3) M), a Na(+)/K(+)-ATPase inhibitor, significantly potentiated NMDA current in rat hippocampal CA1 pyramidal neurons, which was blocked by PP2 (the selective Src tyrosine kinase inhibitor) and PD-98059 [the selective inhibitor of the mitogen-activated protein kinases (MAPK) cascade]. These findings reported here uncover that Src mediates the cross-talk between Na(+)/K(+)-ATPase and NMDA receptor to transduce the signals from Na(+)/K(+)-ATPase to the MAPK cascade and provide new insights into therapeutic target for deeper understanding of the nature of cognitive disorder.
authors.affiliation: Department of Pharmacology, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, Hebei 050017, China. linan_0519@yahoo.com.cn
authors.forename: Linan
authors.initials: L
authors.lastname: Zhang
authors.forename: Fang
authors.initials: F
authors.lastname: Guo
authors.forename: Suwen
authors.initials: S
authors.lastname: Su
authors.forename: Huicai
authors.initials: H
authors.lastname: Guo
authors.forename: Chen
authors.initials: C
authors.lastname: Xiong
authors.forename: Jian
authors.initials: J
authors.lastname: Yin
authors.forename: Wenya
authors.initials: W
authors.lastname: Li
authors.forename: Yongli
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D016202:N-Methylaspartate / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010042:Ouabain / Q000031:analogs & derivatives / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; C000977:dihydroouabain; D010042:Ouabain; D016202:N-Methylaspartate; D019061:src-Family Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D000254:Sodium-Potassium-Exchanging ATPase