ATP potently modulates anion channel-mediated excitatory amino acid release from cultured astrocytes.

ATP potently modulates anion channel-mediated excitatory amino acid release from cultured astrocytes.
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ATP 有效调节阴离子通道介导的培养星形胶质细胞的兴奋性氨基酸释放。

DOI:
10.1152/ajpcell.00438.2001
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发表时间:
2002
期刊:
American journal of physiology. Cell physiology
影响因子:
--
通讯作者:
Kimelberg,HaroldK
Kimelberg,HaroldK
中科院分区:
--
文献类型:
--
作者:
Mongin,AlexanderA;Kimelberg,HaroldK

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体积依赖的ATP释放和随后的嘌呤能P2Y受体的激活被认为是一种自分泌机制,触发了肝癌细胞中体积调节的阴离子通道(VRAC)的激活。在大脑中,三磷酸腺苷由神经元和星形胶质细胞释放,并参与细胞间的通讯。我们探讨了在原代培养的星形胶质细胞中,ATP是否通过VRAC触发或调节兴奋性氨基酸(EaaS)的释放。在基础条件下,外源三磷酸腺苷(10μM)在70-80%的受试培养物中激活了少量的EAA释放。在中度(中等渗透压降低5%)和重度(中等渗透压降低35%)肿胀的星形胶质细胞中,外源性ATP显著促进EAA的释放。ATP的作用可被P2Y激动剂模拟,并被P2Y拮抗剂或ATP清除剂apyrase消除。相反,在没有外源性ATP的情况下,相同的药物操作不能抑制体积依赖的EAA的释放,排除了vrac激活需要自分泌的ATP释放。未肿胀和中度肿胀的细胞中的ATP效应可通过增加5-10%的介质渗透压或阴离子通道阻滞剂来消除,但对破伤风毒素预处理不敏感,进一步支持vrac的参与。我们的数据表明,在星形胶质细胞中,ATP本身并不触发EAA的释放,而是与细胞肿胀协同作用。适度的细胞肿胀和三磷酸腺苷可能是体内神经元-星形胶质细胞双向通讯的两个协同信号。
Volume-dependent ATP release and subsequent activation of purinergic P2Y receptors have been implicated as an autocrine mechanism triggering activation of volume-regulated anion channels (VRACs) in hepatoma cells. In the brain ATP is released by both neurons and astrocytes and participates in intercellular communication. We explored whether ATP triggers or modulates the release of excitatory amino acid (EAAs) via VRACs in astrocytes in primary culture. Under basal conditions exogenous ATP (10 μM) activated a small EAA release in 70–80% of the cultures tested. In both moderately (5% reduction of medium osmolarity) and substantially (35% reduction of medium osmolarity) swollen astrocytes, exogenous ATP greatly potentiated EAA release. The effects of ATP were mimicked by P2Y agonists and eliminated by P2Y antagonists or the ATP scavenger apyrase. In contrast, the same pharmacological maneuvers did not inhibit volume-dependent EAA release in the absence of exogenous ATP, ruling out a requirement of autocrine ATP release for VRAC activation. The ATP effect in nonswollen and moderately swollen cells was eliminated by a 5–10% increase in medium osmolarity or by anion channel blockers but was insensitive to tetanus toxin pretreatment, further supporting VRAC involvement. Our data suggest that in astrocytes ATP does not trigger EAA release itself but acts synergistically with cell swelling. Moderate cell swelling and ATP may serve as two cooperative signals in bidirectional neuron-astrocyte communication in vivo.
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