INOSITOL 1,3,4,5-TETRAKISPHOSPHATE INDUCES CA-2+ SEQUESTRATION IN RAT-LIVER CELLS
INOSITOL 1,3,4,5-TETRAKISPHOSPHATE INDUCES CA-2+ SEQUESTRATION IN RAT-LIVER CELLS
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DOI：
10.1126/science.2847317
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发表时间：
1988-11-25
期刊：
影响因子：
56.9
通讯作者：
BOYNTON, AL
中科院分区：
文献类型：
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作者：
HILL, TD;DEAN, NM;BOYNTON, AL
肌醇1，4，5-三磷酸[I(1，4，5)P3]是与甘油二酯一起产生的第二信使，可与多种生理物质与其细胞表面受体结合。I(，4，5)P3通过受体偶联机制动员细胞内的钙离子，随后增加的细胞内游离钙离子浓度([Ca~(2+)]i)激活了多种细胞反应。电渗性肿瘤大鼠肝上皮细胞(261B)被用来研究钙隔离，这是一种将升高的[Ca~(2+)]i逆转到静止水平并补充细胞内钙池的过程。虽然I(1，4，5)P3动员的Ca~(2+)很容易通过Ca~(2+)-三磷酸腺苷酶的作用被隔离到储存池中，但通过添加非代谢的肌醇三磷酸异构体I(2，4，5)P3动员的Ca~(2+)并不被隔离，这表明代谢是必要的，以消除钙释放的刺激。研究了几种肌醇磷酸化合物降低缓冲[Ca~(2+)]的能力，以确定特定的I(1，4，5)P3代谢物是否可能参与刺激钙离子的固存，其中I(1，3，4，5)P_4单独能诱导钙固存，证明了这种肌醇三磷代谢物的生理作用。
Inositol 1,4,5-triphosphate [I(1,4,5)P3] is a second messenger generated along with diacylglycerol upon the binding of various physiological agents with their cell surface receptors. I(,4,5)P3 mobilizes Ca2+ from intracellular storage sites through a receptor-coupled mechanism, and the subsequent increased intracellular free calcium ion concentration ([Ca2+]i) activates a multitude of cellular responses. Electropermeabilized neoplastic rat liver epithelial (261B) cells were used to study Ca2+ sequestration, a process that reverses the elevated [Ca2+]i to resting levels and replenishes intracellular Ca2+ pools. Although I(1,4,5)P3-mobilized Ca2+ is readily sequestered into storage pools by the action of Ca2+-adenosine triphosphatases, Ca2+ mobilized by addition of the nonmetabolized inositol trisphosphate isomer I(2,4,5)P3 is not sequestered, suggesting that metabolism is necessary to eliminate the stimulus for Ca2+ release. Several inositol phosphate compounds were examined for their ability to lower the buffer [Ca2+] to determine if a specific I(1,4,5)P3 metabolite might be involved in stimulating Ca2+ sequestration; of these, I(1,3,4,5)P4 alone was found to induce Ca2+ sequestration, demonstrating a physiological role for this inositol trisphosphate metabolite.