Inhibitory effect of donepezil on bradykinin-induced increase in the intracellular calcium concentration in cultured cortical astrocytes

Journal of Pharmacological Sciences
Kouki MakitaniToshiaki Kume

Abstract

Donepezil is a potent and selective acetylcholinesterase inhibitor developed for the treatment of Alzheimer's disease. In the present study, we investigated the responses of astrocytes to bradykinin, an inflammatory mediator, and the effect of donepezil on these responses using cultured cortical astrocytes. Bradykinin induced a transient increase of intracellular calcium concentration ([Ca(2+)]i) in cultured astrocytes. Bradykinin-induced [Ca(2+)]i increase was inhibited by the exposure to thapsigargin, which depletes Ca(2+) stores on endoplasmic reticulum, but not by the exclusion of extracellular Ca(2+). Twenty four hours pretreatment of donepezil reduced the bradykinin-induced [Ca(2+)]i increase. This reduction was inhibited not only by mecamylamine, a nAChR antagonist, but also by PI3K and Akt inhibitors. In addition, donepezil inhibited bradykinin-induced increase of the intracellular reactive oxygen species level in astrocytes. These results suggest that donepezil inhibits the inflammatory response induced by bradykinin via nAChR and PI3K-Akt pathway in astrocytes.

Citations

Sep 6, 2018·International Journal of Molecular Sciences·Julia RelatM Victòria Clos
Jan 22, 2019·Nature Neuroscience·Mirko SantelloAndrea Volterra
Jan 13, 2019·British Journal of Pharmacology·Jessica S Sadick, Shane A Liddelow
Jul 1, 2020·Journal of Alzheimer's Disease : JAD·Ricardo B MaccioniNicole Cortés
Aug 11, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Zhenhong LiuPengwen Wang
Jan 10, 2018·Frontiers in Molecular Neuroscience·Rodrigo E González-ReyesLaura Mora-Muñoz

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