Daniell L C, Harris R A
Department of Pharmacology, University of Colorado Health Sciences Center, Denver.
J Pharmacol Exp Ther. 1989 Sep;250(3):875-81.
The effects of ethanol and inositol 1,4,5-trisphosphate (IP3) on releasable Ca stores were examined in microsomes isolated from mouse whole brain. Ca release was monitored by determination of changes in the extra-microsomal Ca concentration using Indo-1, a fluorescent Ca indicator. In the absence of ATP, ethanol released Ca from microsomes in a concentration-dependent manner, with a threshold for Ca release between 25 and 50 mM. Ethanol-induced release of microsomal Ca was reduced by approximately 50% after ATP-stimulated uptake of Ca, indicating that the ethanol-releasable pool was diminished by ATP-dependent uptake of Ca into an ethanol-insensitive microsomal pool. Release of Ca produced by ethanol was linear with concentration (up to 400 mM). By contrast, IP3-induced Ca release was saturable and was dependent on prior ATP-stimulated Ca uptake. Simultaneous addition of ethanol and IP3 produced additive responses. These results show that pharmacologically relevant concentrations of ethanol release Ca from an IP3-insensitive intracellular Ca store. Furthermore, our results demonstrate the existence of at least two releasable stores of Ca in brain microsomes.
在从小鼠全脑分离的微粒体中，研究了乙醇和肌醇1,4,5-三磷酸（IP3）对可释放钙库的影响。使用荧光钙指示剂Indo-1，通过测定微粒体外钙浓度的变化来监测钙释放。在没有ATP的情况下，乙醇以浓度依赖的方式从微粒体中释放钙，钙释放的阈值在25至50 mM之间。在ATP刺激钙摄取后，乙醇诱导的微粒体钙释放减少了约50%，这表明乙醇可释放池因ATP依赖的钙摄取进入乙醇不敏感的微粒体池而减少。乙醇产生的钙释放与浓度呈线性关系（高达400 mM）。相比之下，IP3诱导的钙释放是饱和的，并且依赖于先前ATP刺激的钙摄取。同时添加乙醇和IP3产生相加反应。这些结果表明，药理学相关浓度的乙醇从IP3不敏感的细胞内钙库中释放钙。此外，我们的结果证明了脑微粒体中至少存在两个可释放的钙库。
