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Studies on ATP receptor and K ATP channel to regulate uterine contractility for tocolysis

ATP受体和K ATP通道调节子宫收缩力安胎的研究

基本信息

批准号：
14571564
负责人：
MIYOSHI Hiroshi
金额：
$ 2.24万
依托单位：
Hiroshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571564/
关键词：
uterus ATP receptor P2 receptor patch clamp non selective cation channel perinatal medicine myometrial smooth muscle tocolysis 子宮イオンチャンネル早産治療非選択性陽イオンチャンネル P2チャンネル TRPチャンネルマグネシウムカリウムチャンネル

项目摘要

ATP has been reported to enhance the membrane conductance of myometrial cells and uterine contractions. Some types of ATP (P2X and P2Y) receptor were detected in myometrium using molecular biological methods. However, the role of ATP receptor in regulating uterine contractions is not well understood. ATP receptor currents were recorded from single rat myometrial cells using the whole cell patch clamp method.ATP receptor currents were activated with extracellular ATP in the range of 10,М-1mM.. These currents were in rectangular shapes and should induce membrane depolarizations (pacemaker potentials). ATP receptor had permeability to various monovalent ions and the order of conductance was K^+>Cs^+>Li^+>Na^+. ATP receptor was activated by ADP, GTP, UTP, 2-methylthio ATP and,-methylene ATP by 13 %, 40 %,44 %, 85 %n, and 108 % comparing with ATP of 0.1mM. These currents were blocked by suramin (blocker of P2 receptor) and PPADS (blocker of P2X receptor), indicating P2X receptor is the main component in myometrial cells. Extracellular Mg^<2+> inhibited ATP receptor currents in a dose-dependent manner and the Kd was calculated to be 0.26mM.P2X is the dominant component of ATP receptor in myometrial cells and the currents are thought to induce pacemaker potentials leading to rhythmical uterine contraction in labor. Blocking of ATP receptor may be one of the mechanisms for the inhibition of uterine contractions in tocolysis as reported in studies on myometrial non-selective cation channel.

据报道，三磷酸腺苷可以增强子宫肌层细胞的膜电导和子宫收缩。用分子生物学方法检测了子宫肌层中几种类型的ATP(P2X和P2Y)受体。然而，ATP受体在调节子宫收缩中的作用还不是很清楚。用全细胞膜片钳方法记录单个大鼠子宫肌细胞的ATP受体电流，细胞外三磷酸腺苷在10，М-1 mM范围内激活ATP受体电流。这些电流是矩形的，应该会引起膜去极化(起搏电位)。ATP受体对各种单价离子具有通透性，其电导大小顺序为K^+&GT；Cs+&GT；Li+&GT；Na+。与0.1 mM的ATP相比，ADP、GTP、UTP、2-甲硫基和α-亚甲基ATP分别激活了13%、40%、44%、85%和108%的ATP受体。P2受体阻断剂苏拉明和P2X受体阻滞剂PPADS均能阻断这些电流，提示P2X受体是子宫肌层细胞的主要成分。胞外Mg~(2+)~(2+)以剂量依赖方式抑制ATP受体电流，Kd值为0.26 mM。P2X是子宫肌细胞中ATP受体的主要成分，该电流被认为能诱发起搏电位，导致分娩时子宫节律性收缩。阻断ATP受体可能是肌层非选择性阳离子通道研究中抑制宫缩的机制之一。