Purinergic modulation of pacemaker Ca2+ activity in interstitial cells of Cajal
Purinergic modulation of pacemaker Ca2+ activity in interstitial cells of Cajal
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DOI：
10.1016/j.neuropharm.2004.10.007
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发表时间：
2005-02-01
影响因子：
4.7
通讯作者：
Imaizumi, Y
中科院分区：
文献类型：
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作者：
Furuzono, S;Nakayama, S;Imaizumi, Y
嘌呤受体广泛分布于全身，被认为对许多功能有重要贡献。在这项研究中，我们的特点嘌呤受体的胃肠道自发节律性的机制的贡献。使用从小鼠回肠获得的细胞簇制备物（100 - 200 μ m直径），我们测量了硝苯地平存在下自发的细胞内Ca 2+（[Ca 2 +]（i））振荡，作为Cajal间质细胞（ICCs，c-Kit免疫阳性细胞）中起搏器[Ca 2 +] i活性的指标，所述Cajal间质细胞是胃肠运动的起搏器细胞。这种小制剂还含有平滑肌和肠神经元。使用不同的嘌呤受体激动剂和拮抗剂，我们的特点是TTX敏感和不敏感的调制起搏器[Ca 2 +]（i）的活动在ICC。连续应用ATP、ATP γ S、苏拉明或α，β-亚甲基ATP（α，β-meATP）抑制起搏器[Ca 2 +]（i）活性。预先应用TTX可完全消除α，β-meATP的抑制作用。另一方面，即使在TTX存在的情况下，连续应用浓度大于30 μ M的2-甲硫基ATP（2-MeSATP）引起基线[Ca 2 +] i迅速升高，随后缓慢下降，在下降过程中，起搏[Ca 2 +] i振荡逐渐受到抑制。高浓度（30 - 100 μ M）的UTP和α，β-meATP都没有产生类似的[Ca 2 +]（i）反应。这些结果表明，TTX抗性，直接嘌呤调节的起搏器[Ca 2 +]（i）的活动在ICC介导的P2X嘌呤受体不同的参与TTX敏感的调制。这种缓慢的下降可能是由于这些嘌呤受体的脱敏作用。其他嘌呤受体的可能参与进行了讨论。(C)2004 Elsevier Ltd.保留所有权利。
Purinoceptors are widely distributed throughout the body, and are thought to have important contributions to numerous functions. In this study, we characterised the contribution of purinoceptors to the mechanisms underlying spontaneous rhythmicity of the gastro-intestinal tracts. Using cell cluster preparations (100-200 mum diameter) obtained from murine ileum, we measured spontaneous intracellular Ca2+ ([Ca2+](i)) oscillations in the presence of nifedipine, as an index of pacemaker [Ca2+]i activity in interstitial cells of Cajal (ICCs, c-Kit-immunopositive cells), the pacemaker cells for gastrointestinal motility. This small preparation also contained smooth muscle and enteric neurones. Using various purinoceptor agonists and an antagonist, we characterised both TTX-sensitive and insensitive modulations of pacemaker [Ca2+](i) activity in ICCs. Continuous application of either ATP, ATPgammaS, suramin or alpha,beta-methylene ATP (alpha,beta-meATP) suppressed pacemaker [Ca2+](i) activity. The inhibitory effect of a,p-meATP was completely abolished by a prior application of TTX. On the other hand, even in the presence of TTX, continuous application of 2-methylthio ATP (2-MeSATP) at concentrations greater than 30 muM caused a prompt rise followed by a slow decline of the baseline [Ca2+](i), and pacemaker [Ca2+]i oscillations were gradually suppressed during the decline. Neither UTP nor alpha,beta-meATP at high concentrations (30-100 muM) produced a similar [Ca2+](i) response. These results suggest that the TTX-resistant, direct purinergic modulation of pacemaker [Ca2+](i) activity in ICCs is mediated via P2X purinoceptors distinct from those involved in TTX-sensitive modulation. The slow decline may be attributed to desensitisation of these purinoceptors. The possible involvement of other purinoceptors is also discussed. (C) 2004 Elsevier Ltd. All rights reserved.