Kupffer cells contain a glycine-gated chloride channel
Kupffer cells contain a glycine-gated chloride channel
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DOI：
10.1152/ajpgi.1997.272.6.g1581
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发表时间：
1997-06-01
影响因子：
4.5
通讯作者：
Thurman, RG
中科院分区：
文献类型：
--
作者：
Ikejima, K;Qu, W;Thurman, RG
在这里，甘氨酸对细胞内Ca2+浓度（[Ca2+](i)）的影响，在培养的Kupffer细胞刺激脂多糖（LPS）进行了研究，以评估它们含有甘氨酸门控氯通道的可能性。LPS （10 μ g/ml）快速增加[Ca2+](i)，峰值达到307 +/- 29 nM。甘氨酸（1mm）几乎完全阻止了这种增加。低浓度的士的宁（1 μ M）是一种甘氨酸受体拮抗剂，完全逆转了甘氨酸的抑制作用；然而，高浓度的士的宁（1mm）模拟甘氨酸。将细胞置于无氯化物缓冲液中孵育，可防止甘氨酸和大剂量士的宁对细胞的影响。此外，钾（25 mM）和LPS使Kupffer细胞膜去极化，而甘氨酸引起超极化，并阻止钾和LPS引起的去极化。此外，甘氨酸显著降低了LPS诱导的Kupffer细胞的肿瘤坏死因子- α (tnf - α)的产生。因此，我们得出结论，Kupffer细胞含有一个甘氨酸门控氯通道，类似于先前在中枢神经系统中描述的。通过激活氯离子内流，减少Kupffer细胞毒性介质的合成和释放，预防LPS引起的[Ca2+]增加。
Here the effect of glycine on intracellular Ca2+ concentration ([Ca2+](i)) in cultured Kupffer cells stimulated with lipopolysaccharide (LPS) was investigated to assess the possibility that they contain a glycine-gated chloride channel. LPS (10 mu g/ml) increased [Ca2+](i) rapidly, with peak values reaching 307 +/- 29 nM. Glycine (1 mM) prevented this increase nearly completely. Low concentrations of strychnine (1 mu M), a glycine receptor antagonist, reversed the inhibitory effect of glycine completely; however, high concentrations of strychnine (1 mM) mimicked glycine. The effects of glycine and high-dose strychnine were prevented when cells were incubated in chloride-free buffer. Furthermore, potassium (25 mM) and LPS depolarized the Kupffer cell plasma membrane, whereas glycine caused hyperpolarization and prevented depolarization due to potassium and LPS. Moreover, tumor necrosis factor-alpha (TNF-alpha) production in cultured Kupffer cells due to LPS was decreased significantly by glycine. Therefore, it is concluded that Kupffer cells contain a glycine-gated chloride channel similar to that described previously in the central nervous system. Prevention of increases in [Ca2+](i) due to LPS by activation of chloride influx reduced synthesis and release of toxic mediators by Kupffer cells.