Functional expression of purinergic P2X7 receptors in pregnant rat myometrium
Functional expression of purinergic P2X7 receptors in pregnant rat myometrium
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DOI：
10.1152/ajpregu.00507.2009
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发表时间：
2010-04-01
影响因子：
2.8
通讯作者：
Kudo, Yoshiki
中科院分区：
文献类型：
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作者：
Miyoshi, Hiroshi;Yamaoka, Kaoru;Kudo, Yoshiki
林美美，山冈K，S，小玉M，工藤Y.妊娠大鼠子宫肌嘌呤能P2X7受体的功能表达.Am J Physiol Regul Integr Comp Physiol 298：R1117-R1124,2010.首次发表于2010年1月13日；DOI：10.1152/ajpregu.00507.2009。-三磷酸腺苷已被报道可增强子宫肌层细胞的膜电导和子宫收缩能力。用分子生物学的方法已经报道了嘌呤能P2受体在子宫肌层中的表达，但受体亚型的功能同一性尚未确定。在这项研究中，用全细胞膜片钳技术记录和表征了妊娠大鼠子宫单个肌细胞的ATP诱导电流。细胞外ATP的作用范围为10微米-1毫米，感应电流的EC(50)为74微米，无脱敏、时间依赖性和电压依赖性。感应电流携带多个单价阳离子，电导顺序为K(+)&Gt；Cs(+)&Gt；Li(+)&Gt；Na(+)。它们被P2X受体激动剂激活，其效应顺序为2‘，3’-O-(4-苯甲酰基苯甲酰基)-ATP>；-α-β-亚甲基-ATP>；2-甲硫基-ATP；=UTP>；=GTP>；ADP。选择性P2X7受体拮抗剂3-[5-(2，3-二氯苯基)-1H-四唑-1-基]甲基吡啶(A-438079)可阻断上述电流。因此，我们得出结论，在大鼠子宫肌层细胞中，ATP诱导的电流通过P2X7受体穿过细胞膜。我们进一步证明，细胞外的镁离子(IC(50)=0.26 mM)可阻断ATP诱导的电流。临床上，服用细胞外镁(2+)可以抑制子宫收缩。因此，子宫收缩可能是由细胞外ATP升高引起的，而通过镁(2+)抑制P2X7受体而抑制。需要进一步研究P2X7受体作为异常子宫收缩的治疗靶点，作为治疗早产的可能方法。
Miyoshi H, Yamaoka K, Urabe S, Kodama M, Kudo Y. Functional expression of purinergic P2X7 receptors in pregnant rat myometrium. Am J Physiol Regul Integr Comp Physiol 298: R1117-R1124, 2010. First published January 13, 2010; doi: 10.1152/ajpregu.00507.2009.-ATP has been reported to enhance the membrane conductance of myometrial cells and uterine contractility. Purinergic P2 receptor expression has been reported in the myometrium, using molecular biology, but the functional identity of the receptor subtype has not been determined. In this study, ATP-induced currents were recorded and characterized in single myometrial cells from pregnant rats using whole cell patch clamping. Extracellular ATP was applied in the range of 10 mu M-1 mM and induced currents with an EC(50) of 74 mu M, with no desensitization, time dependency, or voltage dependency. The currents induced carried multiple monovalent cations, with conductances ranked as K(+) > Cs(+) > Li(+) > Na(+). They were activated by P2X receptor agonists, with their effectiveness ranked as 2',3'-O-(4-benzoylbenzoyl)-ATP >> ATP > alpha beta-methylene-ATP > 2-methyl-thio ATP >= UTP >= GTP > ADP. These currents were blocked by the selective P2X7 receptor antagonist 3-[5-(2,3-dichlorophenyl)-1 H-tetrazol-1-yl]methyl pyridine (A-438079). We therefore concluded that ATP-induced currents in rat myometrial cells crossed cell membranes via P2X7 receptors. We further showed that the ATP-induced currents were blocked by extracellular Mg(2+) (IC(50) = 0.26 mM). Clinically, administering extracellular Mg(2+) is known to inhibit uterine contraction. It therefore seems likely that uterine contraction may be induced by raised extracellular ATP and suppressed via Mg(2+) inhibiting P2X7 receptors. Further research is needed into the P2X7 receptor as a therapeutic target in abnormal uterine contraction, as a possible treatment for premature labor.