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禁食后再喂养刺激的大鼠视上核中P2X2受体表达及功能上调

P2X2 Receptor Expression and Function Is Upregulated in the Rat Supraoptic Nucleus Stimulated Through Refeeding After Fasting.

作者信息

Ivetic Milorad, Bhattacharyya Anirban, Zemkova Hana

机构信息

Department of Cellular and Molecular Neuroendocrinology, Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czechia.

出版信息

Front Cell Neurosci. 2019 Jun 26;13:284. doi: 10.3389/fncel.2019.00284. eCollection 2019.

Abstract

Magnocellular neurons in the supraoptic nucleus (SON), which synthesize and release arginine vasopressin (AVP) and oxytocin (OT), express several subtypes of ATP-stimulated purinergic P2X receptors (P2XR) that modulate neuronal activity as well as neurotransmitter and hormone release. However, the physiological impact of this modulation is not well understood. Here, we tested a hypothesis that P2XRs play a role in the sustained release of hormones from SON neurons stimulated through fasting/refeeding. We studied the effect of 2 h of refeeding after 48 h of fasting on P2XR and P2YR mRNA expression and ATP-induced presynaptic and postsynaptic responses in the SON of 30-day-old rats. Quantitative real-time PCR revealed that the expression of P2X2R and AVP mRNA was upregulated, whereas P2X4R, P2X7R, P2Y2R, and OT mRNA levels were not significantly changed and P2Y1R mRNA expression was decreased. Whole-cell patch clamp recordings performed on isolated rat brain slices showed that the amplitude of the ATP-stimulated somatic current and the ATP-induced increases in the frequency of spontaneous GABAergic inhibitory postsynaptic currents were significantly higher in SON neurons from fasted/refed rats than in SON neurons from normally fed rats. No evidence was found for changes in the presynaptic effect of ATP in SON neurons not expressing somatic P2XRs. These results suggest that the increased activity of SON neurons synthesizing AVP is associated with enhanced expression of P2X2Rs on neuronal cell bodies and their GABAergic presynaptic nerve terminals.

摘要

视上核(SON)中的大细胞神经元可合成并释放精氨酸加压素(AVP)和催产素(OT),这些神经元表达多种ATP刺激的嘌呤能P2X受体(P2XR)亚型,这些受体可调节神经元活动以及神经递质和激素的释放。然而,这种调节的生理影响尚未得到充分了解。在此,我们测试了一个假设,即P2XRs在禁食/再喂养刺激的SON神经元激素持续释放中发挥作用。我们研究了禁食48小时后2小时再喂养对30日龄大鼠SON中P2XR和P2YR mRNA表达以及ATP诱导的突触前和突触后反应的影响。定量实时PCR显示,P2X2R和AVP mRNA的表达上调,而P2X4R、P2X7R、P2Y2R和OT mRNA水平没有显著变化,P2Y1R mRNA表达下降。对分离的大鼠脑片进行的全细胞膜片钳记录显示,禁食/再喂养大鼠的SON神经元中,ATP刺激的体细胞电流幅度和ATP诱导的自发性GABA能抑制性突触后电流频率增加显著高于正常喂养大鼠的SON神经元。在不表达体细胞P2XRs的SON神经元中,未发现ATP突触前效应有变化的证据。这些结果表明,合成AVP的SON神经元活性增加与神经元细胞体及其GABA能突触前神经末梢上P2X2Rs表达增强有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1759/6607214/3afdf91f6fe1/fncel-13-00284-g001.jpg

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