P2 receptors in the murine gastrointestinal tract
P2 receptors in the murine gastrointestinal tract
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DOI：
10.1016/s0028-3908(02)00294-0
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发表时间：
2002-12-01
影响因子：
4.7
通讯作者：
Burnstock, G
中科院分区：
文献类型：
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作者：
Giaroni, C;Knight, GE;Burnstock, G
研究了腺苷、腺苷 5'-三磷酸 (ATP)、2-甲硫基腺苷二磷酸 ADP (2-MeSADP)、2-甲硫基 ATP (2-MeSATP)、α,β-亚甲基 ATP (α,β-meATP) 和尿苷三磷酸 (UTP) 对小鼠胃（胃底）、十二指肠、回肠和结肠分离片段的作用。采用免疫组织化学方法检测P2Y(1)、P2Y(2)、P2Y(4)、P2X(1)和P2X(2)受体及神经元一氧化氮合酶(NOS)的定位，并采用原位杂交检测P2Y(1) mRNA。所有区域的纵向肌肉松弛效力的顺序为：2-MeSADP大于或等于2-MeSATP>α，β-meATP>ATP=UTP=腺苷。这表明 P2Y(1) 介导的松弛以及可能对 α,β-meATP 敏感的进一步 P2Y 受体亚型。由于 ATP 和 UTP 是等价的，因此表明存在 P2Y(2) 受体。 ATP 反应被 P2Y(1) 选择性拮抗剂 MRS 2179 和苏拉明抑制。通过免疫组织化学法观察回肠平滑肌和肌间神经元亚群中的 P2Y(1) 受体，这些受体也对 NOS 进行了染色。 P2Y，mRNA 定位于回肠肌间神经节和粘膜下神经节的神经元中。总而言之，这些结果表明 ATP 作用于非肾上腺素能、非胆碱能抑制性神经元，这些神经元释放一氧化氮 (NO) 和 ATP。河豚毒素和 N-w-硝基-L-精氨酸甲酯对 2-MeSADP 的松弛作用减少，与这种可能性一致。腺苷通过 P1 受体发挥作用，放松小鼠肠道的平滑肌。小鼠结肠段（与胃和小肠相反）被核苷酸以效力顺序收缩：2-MeSATP > (x,p-meATP > ATP；收缩没有表现出脱敏作用，并被苏拉明和 PPADS 拮抗，与 P2X2 受体介导的反应一致。在结肠的纵向和环肌上都显示出对 P2X2 受体的免疫反应性，但在肠道的其他区域中没有显示出对 P2X2 受体的免疫反应性。总之，神经元 P2Y(1) 受体似乎主要通过小鼠肠道所有区域的 NO 介导松弛，在较小程度上通过 P2Y(1)、P2Y(2) 和平滑肌中对 α,β-meATP 敏感的新型 P2Y 受体亚型介导，而 P2X(2) 受体介导结肠平滑肌的收缩 (C) 2002 Elsevier Science。有限公司保留所有权利。
The actions of adenosine, adenosine 5'-triphosphate (ATP), 2-methylthio adenosine diphosphate ADP (2-MeSADP), 2-methylthio ATP (2-MeSATP), alpha,beta-methylene ATP (alpha,beta-meATP) and uridine triphosphate (UTP) on isolated segments of mouse stomach (fundus), duodenum, ileum and colon were investigated. The localization of P2Y(1), P2Y(2), P2Y(4), P2X(1) and P2X(2) receptors and neuronal nitric oxide synthase (NOS) were examined immunohistochemically, and P2Y(1) mRNA was examined with in situ hybridization. The order of potency for relaxation of longitudinal muscle of all regions was: 2-MeSADP greater than or equal to 2-MeSATP > alpha,beta-meATP > ATP = UTP = adenosine. This is suggestive of P2Y(1)-mediated relaxation and perhaps a further P2Y receptor subtype sensitive to alpha,beta-meATP. As ATP and UTP are equipotent, the presence of a P2Y(2) receptor is indicated. ATP responses were inhibited by the P2Y(1)-selective antagonist MRS 2179, and suramin. P2Y(1) receptors were visualized immunohistochemically in the smooth muscle of the ileum and in a subpopulation for myenteric neurones, which also stained for NOS. P2Y, mRNA was localized in neurones in both myenteric and submucosal ganglia in the ileum. Taken together, these results suggest that ATP was acting on non-adrenergic, non-cholinergic inhibitory neurons, which release both nitric oxide (NO) and ATP. Reduced relaxations to 2-MeSADP by tetrodotoxin and N-w-nitro-L-arginine methyl ester, are consistent with this possibility. Adenosine acts via P1 receptors to relax smooth muscle of the mouse gut. Segments of mouse colon (in contrast to the stomach and small intestine) were contracted by nucleotides with the potency order: 2-MeSATP > (x,p-meATP > ATP; the contractions showed no desensitization and were antagonized by suramin and PPADS, consistent with responses mediated by P2X2 receptors. Immunoreactivity to P2X2 receptors was demonstrated on both longitudinal and circular muscle of the colon, but not in the other regions of the gut, except for a small subpopulation of myenteric neurones. In summary, neuronal P2Y(1) receptors appear to mediate relaxation, largely through NO in all regions of the mouse gut, and to a lesser extent by P2Y(1), P2Y(2) and a novel P2Y receptor subtype responsive to alpha,beta-meATP in smooth muscle, while P2X(2) receptors mediate contraction of colonic smooth muscle. (C) 2002 Elsevier Science Ltd. All rights reserved.