Possible Mechanism of Effects of Etimicin and Gentamicin on Intracellular Calcium Homeostasis  

爱大霉素和庆大霉素对胞浆Ca^(2+)影响的初步机制(英文)

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作  者:李忠东[1] 王建昌[1] 李培忠[2] 

机构地区:[1]空军总医院,北京100036 [2]军事医学科学院毒物药物研究所,北京100850

出  处:《Journal of Chinese Pharmaceutical Sciences》2005年第2期131-134,共4页中国药学(英文版)

摘  要:Aim Intracellular calcium ([Ca^(2+) ]_i) is mainly regulated by mitochondriaand endo-plasmic reticula. This study was carried out to ascertain whether the elementary mechanismof the effects of etimicin (EM) and gentamicin (GM) on [Ca^(2+) ]_i is related to their effects onmitochondrion Ca^(2+) -uptake and endoplasmic reticulum Ca^(2+) -uptake. Methods The effects of GMand EM on [Ca^(2+) ]_i in LLC-PK1 were determined with a fluorescent probe of Fura-2/AM. The effectsof EM and GM on mitochondrion Ca^(2+) -uptake and endoplasmic reticulum Ca^(2+) -uptake weredetermined by isotope indicator (^(45)Ca^(2+) ) . Results EM and GM at the concentration of 1mmol·L^(-1) had no significant effect on [Ca^(2+) ]_i(P. > 0.05) and at 10 mmol·L^(-1)significantly caused [Ca^(2+) ]_i to increase (P < 0.01). EM and GM at 1 mmol·L^(-1) causedmitochondrion Ca^(2+)-uptake to ascend dramatically (P < 0.05) and at 10 mmol·L^(-1) causedmitochondrion Ca^(2+) -uptake to descend significantly. EM and GM at more than 0.34 mrnol·L^(-1)significantly inhibited endoplasmic reticulum Ca^(2+) -uptake (P < 0.05 or 0.01). Conclusion Novariation of [Ca^(2+) ]_i caused by EM and GM at lower concentrations might relate to theequilibrium of their promotion of mitochondrion Ca^(2+) -uptake with their inhibition of endoplasmicreticulum Ca^(2+) -uptake. The elevation of [Ca^(2+) ]_i caused by EM and GM at higherconcentrations might correlate with their inhibition of mitochondrion Ca^(2+) -uptake andendoplasmic reticulum Ca^(2+) -uptake.目的观察爱大霉素(EM)和庆大霉素(GM)对胞浆Ca2+影响的初步机制。方法以Fura2/AM为探针测定EM和GM在不同浓度时对LLCPK1肾上皮细胞浆Ca2+的影响,同位素示踪法测定EM和GM对线粒体Ca2+摄取和内质网Ca2+摄取的影响。结果EM和GM在1mmol·L-1时对胞浆Ca2+浓度无显著影响,P>0.05;在10mmol·L-1时可使胞浆Ca2+显著上升,P<0.01。EM和GM在1mmol·L-1时显著促进线粒体Ca2+摄取(P<0.05);在10mmol·L-1时,二者显著抑制线粒体Ca2+摄取。EM和GM在>0.34mmol·L-1时显著抑制内质网Ca2+摄取(P<0.05或0.01)。结论低浓度EM和GM未能引起胞浆Ca2+升高可能与其促进线粒体Ca2+摄取与抑制内质网Ca2+摄取相互平衡有关;高浓度EM和GM引起胞浆Ca2+升高可能与其均抑制线粒体和内质网Ca2+摄取有关。

关 键 词:ETIMICIN GENTAMICIN ca^(2+) homeostasis MITOCHONDRIA endoplasmic reticula 

分 类 号:R96[医药卫生—药理学]

 

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