Molecular mechanism of excitatory effect of adenosine on neurotransmission

腺苷对神经传递兴奋作用的分子机制

基本信息

  • 批准号:
    07680895
  • 负责人:
  • 金额:
    $ 1.54万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    1995
  • 资助国家:
    日本
  • 起止时间:
    1995 至 1996
  • 项目状态:
    已结题

项目摘要

Adenosine, an endogenous brain substance is considered to be an inhibitory and excitatory neuromodulator in neurotansmission in the central nervous system. The mechanism of excitatory effect of adenosine has not yet been studied in detail. The purpose of the present experiment was to clarify the mechanism of excitatory effect of adenosine using the superior colliculus of the rat in which adenosine shows potent excitatory effect on neurotransmission.(1) Study using in vivo preparation of the rat.The application of adenosine in the vicinity of recording electrode enhanced the synaptic potential (150-170% of original level) evoked in the superficial gray layr of the superior colliculus after electrical stimulation to optic nerve. Systemic application of EHNA,an adenosine diaminase inhibitor, also enhanced the synaptic potential as observed in the topical application of adenosine as mentioned above. Usig microdialysis technique, glutamate release, an excitatory transmitter in this region w … More as determined during application of adenosine or EHNA.Application of EHNA and topical application of adenosine increased the release of glutamate (130%) in the dialisate.(2) Effect of adenosine on isolated cultured neuron of superior colliculus.To test the postsynaptic effect of adenosine, its effect on the isolated cultured superior colliculus neuron was investigated using whole cell patch clamp method. The K^+-conductance of the membrane was increased by application of adenosine. By applying agonists and antagonists of adenosine receptors, this effect was found to be mediated through P_<2Y> receptor.(3) Involvement of A_<2A> receptors of the excitatory effect of adenosine.The excitatory effect of adenosine or EHNA was blocked by the A_<2A> antagonist, KF17837 whereas it was not counteracted by the DPCPX,an A_1 antagonist. By the TR-PCR method, the presence of A_2 mRNA was found in the superior colliculus.These results indicate that the excitatory effect of adenosine in the superior colliculus was mediated through A_<2A> receptor which enhance presynaptically the release of glutamate, whereas there is a possibility that adenosine may inhibit the postsynaptic activity by increasing the K^+-conductance, and this can be apparently masked by presynaptic excitatory action of adenosine. Less
腺苷是一种内源性脑内物质,在中枢神经系统的神经传递中被认为是一种抑制性和兴奋性的神经调质。腺苷兴奋作用的机制尚未详细研究。本实验的目的是利用腺苷对神经传递具有强兴奋作用的大鼠上级丘来阐明腺苷兴奋作用的机制。(1)用大鼠在体标本进行研究。在记录电极附近应用腺苷,可使电刺激视神经后在上级丘浅灰质层诱发的突触电位增强150-170%。全身应用腺苷二氨酶抑制剂EHNA也增强了突触电位,如在上述腺苷局部应用中所观察到的。利用微透析技术,在此区域的兴奋性递质谷氨酸的释放, ...更多信息 应用EHNA和局部应用腺苷增加了二磺酸盐中谷氨酸的释放(130%)。(2)腺苷对离体培养上级丘神经元的作用:采用全细胞膜片钳技术观察腺苷对离体培养上级丘神经元的突触后作用。膜的K^+电导率通过腺苷的应用而增加。通过应用腺苷受体激动剂和拮抗剂,发现这种作用是通过P受体介导<2Y>的。(3)腺苷兴奋作用的A受体参与<2A>腺苷或EHNA的兴奋作用可被A受体<2A>拮抗剂KF 17837阻断,而不能被A_1受体拮抗剂DPCPX拮抗。用TR-PCR方法在上级丘中检测到A_2mRNA的存在,提示腺苷对上级丘的兴奋作用是通过A_受体介导<2A>的,它能促进突触前谷氨酸的释放,而腺苷可能通过增加K^+传导抑制突触后活动。并且这可以明显地被腺苷的突触前兴奋作用掩盖。少

项目成果

期刊论文数量(21)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Y. Ikeuchi, T. Nishizaki, M. Mori, Y. Okada: "Adenosine activates the K^+ channel and enhances cytosolic Ca^<2+> release via a P_<2Y> purinoceptor in hippocampal neurons" Eur. J. Pharmacol.304. 191-199 (1996)
Y. Ikeuchi、T. Nishizaki、M. Mori、Y. Okada:“腺苷激活 K^ 通道并通过海马神经元中的 P_<2Y> 嘌呤受体增强胞质 Ca^<2> 释放”Eur。
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  • 影响因子:
    0
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  • 通讯作者:
H. Hirai, Y. Ikeuchi, Y. Okada: "The contribution of PKA to the excitatory mechanism of adenosine in guinea pig superior colliculus slices" Neurosci. Lett.182. 33-36 (1994)
H. Hirai、Y. Ikeuchi、Y. Okada:“PKA 对豚鼠上丘切片中腺苷兴奋机制的贡献” Neurosci。
  • DOI:
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  • 影响因子:
    0
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  • 通讯作者:
H.Hirai,Y.Ikeuchi,Y.Okada: "The contribution of PKA to the excitatory mechanism of adenosine in guinea pig superior colliculus slices" Neurosci.Lett.182. 33-36 (1994)
H.Hirai、Y.Ikeuchi、Y.Okada:“PKA 对豚鼠上丘切片中腺苷兴奋机制的贡献” Neurosci.Lett.182。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Youji Ikeuchi: "Adenosine activates the potassium channel via a P_2 purinoceptor but not via an adenosine receptorin cultured rat superior colliculus neurons" Neuroscience Letters. 198. 205-208 (1995)
Youji Ikeuchi:“在培养的大鼠上丘神经元中,腺苷通过 P_2 嘌呤受体激活钾通道,但不通过腺苷受体激活”《神经科学快报》。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Youji Ikeuchi, Tomoyuki Nishizaki, Masahiro Mori, Yasuhiro Okada: "Adenosine activates the K^+ channel and enhances cytosolic Ca^<2+> release via a P_<2Y> purinoceptor in hippocampal neurons" Eur.J.Pharmacol.304. 191-199 (1996)
Youji Ikeuchi、Tomoyuki Nishizaki、Masahiro Mori、Yasuhiro Okada:“腺苷激活 K^ 通道并通过海马神经元中的 P_<2Y> 嘌呤受体增强胞质 Ca^<2> 释放”Eur.J.Pharmacol.304。
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    0
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OKADA Yasuhiro其他文献

OKADA Yasuhiro的其他文献

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{{ truncateString('OKADA Yasuhiro', 18)}}的其他基金

Search for a new elementary particle picture at the TeV scale through flavor physics
通过风味物理学寻找 TeV 尺度的新基本粒子图像
  • 批准号:
    20244037
  • 财政年份:
    2008
  • 资助金额:
    $ 1.54万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Exploration of physics beyond the standard model through flavor physics
通过风味物理学探索标准模型之外的物理学
  • 批准号:
    17540286
  • 财政年份:
    2005
  • 资助金额:
    $ 1.54万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Phenomenological study of supersymmetric models
超对称模型的唯象研究
  • 批准号:
    16081211
  • 财政年份:
    2004
  • 资助金额:
    $ 1.54万
  • 项目类别:
    Grant-in-Aid for Scientific Research on Priority Areas
Flavor physics in supersymmetric models
超对称模型中的风味物理
  • 批准号:
    13640309
  • 财政年份:
    2001
  • 资助金额:
    $ 1.54万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Phenomenology of Supersymmetric Grand Unified Theories and Standard Model
超对称大统一理论和标准模型的现象学
  • 批准号:
    10209210
  • 财政年份:
    1998
  • 资助金额:
    $ 1.54万
  • 项目类别:
    Grant-in-Aid for Scientific Research on Priority Areas (B)
Lepton Flavor Violating Processes in Supersymmetric Models
超对称模型中的轻子味破坏过程
  • 批准号:
    09640381
  • 财政年份:
    1997
  • 资助金额:
    $ 1.54万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Supersymmmetric theory and bottom quark physics
超对称理论和底夸克物理
  • 批准号:
    06640422
  • 财政年份:
    1994
  • 资助金额:
    $ 1.54万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Unification Theories Including Gravity and its Mathematical Structure
包括重力及其数学结构在内的统一理论
  • 批准号:
    02044015
  • 财政年份:
    1990
  • 资助金额:
    $ 1.54万
  • 项目类别:
    Grant-in-Aid for international Scientific Research

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