GLUCONEOGENESIS STIMULATED BY EXTRACELLULAR ATP IS TRIGGERED BY THE INITIAL INCREASE IN THE INTRACELLULAR CA2+ CONCENTRATION OF THE PERIPHERY OF HEPATOCYTES
GLUCONEOGENESIS STIMULATED BY EXTRACELLULAR ATP IS TRIGGERED BY THE INITIAL INCREASE IN THE INTRACELLULAR CA2+ CONCENTRATION OF THE PERIPHERY OF HEPATOCYTES
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DOI：
10.1042/bj2830265
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发表时间：
1992-04-01
影响因子：
4.1
通讯作者：
TAKEGUCHI, N
中科院分区：
文献类型：
--
作者：
KOIKE, M;KASHIWAGURA, T;TAKEGUCHI, N
细胞外 ATP、ADP 和 GTP 增加了离体大鼠肝细胞悬液中的细胞内游离 Ca2+ 浓度 ([Ca2+]i)。 通过测定fura-2荧光测定[Ca2+]i，其增加呈双相性。 最初的短暂上升之后是一个更持久的平台期。 早期部分的峰值先于第二部分的稳定水平。 100-mu-M-ATP 下单细胞中 [Ca2+]i 变化的时间过程与悬浮系统中观察到的非常相似。 用 40 mM 咖啡因、2 mM 草酸盐或 60-mu-M-丹曲林钠预孵育肝细胞可抑制 P2 嘌呤能反应。 在细胞外 100-mu-M-LaCl3 存在或细胞外 Ca2+ 不存在的情况下测量时，未观察到平台期。 还通过荧光图像分析确定了单个肝细胞中[Ca2+]i的分布。 在初始阶段，[Ca2+]i 的增加在细胞的外围区域比中心区域更大。 测量肝细胞悬液中胞外 ATP 酶对细胞外 ATP 的降解；在测量细胞悬液中的细胞内[Ca2+]i过程中，ATP降解量小于初始量（100-mu-M）的10-15%。 细胞外 ATP 刺激葡萄糖合成。 葡萄糖生成速率也显示出两个组成部分，即 1 分钟内的初始快速组成部分和随后的较慢组成部分。 初始快速成分的速率不取决于细胞外 Ca2+ 的存在或不存在，而后续成分的速率则取决于细胞外 Ca2+。 本研究表明，[Ca2+]i 的初始短暂升高在触发糖异生中起着重要作用。
Extracellular ATP, ADP and GTP increased the intracellular free Ca2+ concentration ([Ca2+]i) in a suspension of isolated rat hepatocytes. The [Ca2+]i was determined by measuring fura-2 fluorescence, and its increase was biphasic. The initial transient rise was followed by a longer-lasting plateau. The peak of the early component preceded the plateau level of the second component. A time course of change in [Ca2+]i in single cells at 100-mu-M-ATP was very similar to that observed in the suspension system. Preincubation of hepatocytes with 40 mM-caffeine, 2 mM-oxalate or 60-mu-M-dantrolene sodium inhibited the P2 purinergic response. The plateau phase was not observed when measured in the presence of extracellular 100-mu-M-LaCl3 or in the absence of extracellular Ca2+. The distribution of [Ca2+]i in single hepatocytes was also determined by fluorescence image analysis. In the initial phase, the increase in [Ca2+]i is greater in the peripheral region than the central region of the cell. Degradation of extracellular ATP by ecto-ATPase in the hepatocyte suspension was measured; the amount of ATP degradation was less than 10-15% of the initial amount (100-mu-M) during the measurement of the intracellular [Ca2+]i in the cell suspension. Extracellular ATP stimulated glucose synthesis. The rate of glucose production also showed two components, the initial fast component within 1 min and the subsequent slower component. The rate of the initial fast component did not depend on the presence or absence of extracellular Ca2+, whereas the rate of the subsequent component depended on it. The present study shows that the initial transient rise in [Ca2+]i plays an important role in triggering the gluconeogenesis.