title: Simvastatin inhibits acidic extracellular pH-activated, outward rectifying chloride currents in RAW264.7 monocytic-macrophage and human peripheral monocytes.
abstract: Extracellular acidic pH activated chloride channels (I(Cl,acid)) have been characterized in HEK 293 cells and mammalian cardiac myocytes. This study was designed to evaluate the expression of I(Cl,acid) in RAW264.7 monocytic-macrophage and human peripheral monocytes and to investigate the effect of simvastatin on I(Cl,acid). In two kinds of cells, the activation and deactivation of the current rapidly and repeatedly followed the change of the extracellular solution to pH=4.3. Compared with the outward current (pA/pF) activated at pH 4.3, the currents inhibited by simvastatin at concentrations of 0.1 microM were all decreased a little, however the currents at concentrations of 1 microM and 10 microM simvastatin were decreased significantly. The IC(50) for simvastatin inhibiting I(Cl,acid) of RAW264.7 was 13.77 microM. In summary, we report for the first time that simvastatin inhibits the I(Cl,acid) of RAW264.7 monocytic-macrophage and human peripheral monocytes in a concentration-dependent manner.
authors.affiliation: Department of Pharmacy, QiLu Hospital, Shandong University, Jinan 250012, China.
authors.forename: Cheng-Yao
authors.initials: CY
authors.lastname: Shi
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Chun-Xi
authors.initials: CX
authors.lastname: Liu
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Ma
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002460:Cell Line; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D018118:Chloride Channels; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin