ATP increases intracellular calcium in supraoptic neurons by activation of both P2X and P2Y purinergic receptors.
ATP increases intracellular calcium in supraoptic neurons by activation of both P2X and P2Y purinergic receptors.
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ATP 通过激活 P2X 和 P2Y 嘌呤受体来增加视上神经元的细胞内钙。
DOI：
10.1152/ajpregu.00495.2006
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Sladek,CeliaD
中科院分区：
文献类型：
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作者：
Song,Zhilin;Vijayaraghavan,Sukumar;Sladek,CeliaD
ATP可增加下丘脑-神经垂体系统移植物中视上核（SON）神经元内钙离子浓度（[Ca ~（2+）]i）。预计P2 X嘌呤能受体（P2 XR）参与这种反应，因为ATP刺激下丘脑-神经垂体系统外植体释放加压素需要激活P2 XR，而P2 XR的激活诱导解离SON神经元中[Ca 2 +] i的增加。ATP诱导的[Ca ~（2+）]_o升高在去除灌流液中Ca ~（2+）后仍持续。这表明P2 Y嘌呤能受体（P2 YR）的参与，因为P2 YR诱导Ca 2+从细胞内储存释放，而P2 XR是Ca 2+渗透性离子通道。用毒胡萝卜素（TG）耗竭[Ca ~（2+）] i库可阻止ATP诱导的[Ca ~（2+）] i增加，但在2 mM [Ca ~（2+）]o中不能，表明细胞内Ca ~（2+）内流和释放都有助于ATP反应。镉可部分阻断Ca 2+内流，表明电压门控Ca 2+通道的贡献。PPADS（吡哆醛磷酸-6-偶氮苯基-2 ′，4 ′-二磺酸）和iso-PPADS（P2 XR拮抗剂）减弱但不能消除ATP诱导的[Ca 2 +]i增加。PPADS或iso-PPADS与TG联合治疗可防止反应。由UTP、UDP和2-甲硫基-ADP组成的P2 YR激动剂的混合物增加[Ca 2 +]i（有或没有河豚毒素），而TG显著减弱[Ca 2 +]i。2-Methylthio-ADP单独诱导的[Ca ~（2+）] i增加幅度大于UTP或UDP。P2 Y1 R特异性拮抗剂MRS 2179可消除ATP对细胞内[Ca ~（2+）]o为零的反应。因此，P2 XR和P2 YR都参与了ATP诱导的[Ca 2 +]i增加，并且P2 Y1 R亚型在SON中比P2 Y2 R、P2 Y 4 R或P2 Y 6 R更突出。
ATP increases intracellular calcium concentration ([Ca2+]i) in supraoptic nucleus (SON) neurons in hypothalamo-neurohypophyseal system explants loaded with the Ca2+-sensitive dye, fura 2-AM. Involvement of P2X purinergic receptors (P2XR) in this response was anticipated, because ATP stimulation of vasopressin release from hypothalamo-neurohypophyseal system explants required activation of P2XRs, and activation of P2XRs induced an increase in [Ca2+]iin dissociated SON neurons. However, the ATP-induced increase in [Ca2+]ipersisted after removal of Ca2+from the perifusate ([Ca2+]o). This suggested involvement of P2Y purinergic receptors (P2YR), because P2YRs induce Ca2+release from intracellular stores, whereas P2XRs are Ca2+-permeable ion channels. Depletion of [Ca2+]istores with thapsigargin (TG) prevented the ATP-induced increase in [Ca2+]iin zero, but not in 2 mM [Ca2+]o, indicating that both Ca2+influx and release of intracellular Ca2+contribute to the ATP response. Ca2+influx was partially blocked by cadmium, indicating a contribution of voltage-gated Ca2+channels. PPADS (pyridoxal-phosphate-6-azophenyl-2′,4′-disulphonic acid), and iso-PPADS, P2XR antagonists, attenuated, but did not abolish, the ATP-induced increase in [Ca2+]i. Combined treatment with PPADS or iso-PPADS and TG prevented the response. A cocktail of P2YR agonists consisting of UTP, UDP, and 2-methylthio-ADP increased [Ca2+]i(with or without tetrodotoxin) that was markedly attenuated by TG. 2-Methylthio-ADP alone induced consistent and larger increases in [Ca2+]ithan UTP or UDP. MRS2179, a specific P2Y1R antagonist, eliminated the response to ATP in zero [Ca2+]o. Thus, both P2XR and P2YR participate in the ATP-induced increase in [Ca2+]i, and the P2Y1R subtype is more prominent than P2Y2R, P2Y4R, or P2Y6R in SON.