NO-induced relaxation of labouring and non-labouring human myometrium is not mediated by cyclic GMP
NO-induced relaxation of labouring and non-labouring human myometrium is not mediated by cyclic GMP
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DOI：
10.1038/sj.bjp.0704226
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发表时间：
2001-09-01
影响因子：
7.3
通讯作者：
Tichenor, S
中科院分区：
文献类型：
--
作者：
Buxton, ILO;Kaiser, RA;Tichenor, S
1. 在来自足月未临产人子宫的子宫肌条中，添加催产素（OT）可诱发剂量依赖性（10 - 3000 nM）的阶段性收缩，这种收缩可被阿托西班（1 μM）拮抗，并可因添加一氧化氮供体S - 亚硝基 - L - 半胱氨酸（Cys - NO）而松弛。然而，在足月临产的子宫肌中，添加OT对于增加额外张力无效。
2. 在临产和未临产组织中，Cys - NO介导的自发收缩或OT诱导收缩的松弛作用（半数抑制浓度IC50 = 1 μM）不受预先添加鸟苷酸环化酶（GC）抑制剂ODQ（1H - [1,2,4]恶二唑并[4,3 -α]喹喔啉 - 1 - 酮；1 μM）或亚甲蓝（MB；10 μM）的影响。
3. 在未临产组织中伴随30 μM Cys - NO添加而升高的细胞内环鸟苷酸（7.5倍）以及在临产组织中（2.5倍），在预先用ODQ或MB处理过的组织中完全被阻断。
4. 蝎毒素（ChTx）、伊比利亚蝎毒素（IbTx）和卡利蝎毒素（KalTx）都使Cys - NO抑制曲线右移，并降低最大Cys - NO处理所产生的松弛程度（在未临产组织中为100 μM；在临产组织中，KalTx阻止了Cys - NO在受刺激和未受刺激组织中介导的松弛作用）。
5. 添加一氧化氮供体S - 亚硝基 - N - 乙酰青霉胺（SNAP）可使妊娠子宫肌产生剂量依赖性松弛，而3 - 吗啉代斯德酮亚胺（SIN - 1）则无此作用。SIN - 1未能松弛OT诱导的收缩并非由于供体未能刺激子宫肌鸟苷酸环化酶。
6. 我们证明，尽管一氧化氮有刺激妊娠子宫肌鸟苷酸环化酶的能力，但松弛作用与环鸟苷酸的作用无关。钾离子通道抑制剂的作用表明，一氧化氮诱导的人子宫平滑肌松弛可能是通过直接或间接激活一个或多个钙激活钾离子通道来实现的。
1 In myometrial strips from near-term non-labouring human uterus, addition of oxytocin (OT) evoked dose-dependent (10 - 3000 nM) phasic contractions that were antagonized by atosiban (1 muM) and relaxed by addition of the nitric oxide donor S-nitroso L-cysteine (Cys-NO). In near-term labouring myometrium, however, addition of OT was ineffective at raising additional tone.2 In both labouring and non-labouring tissue, Cys-NO mediated relaxation of spontaneous or OT-induced contractions (IC50 = 1 muM) was unaffected by prior addition of the guanylyl cyclase (GC) inhibitors ODQ (1H-[1,2,4]oxadiazolo[4,3,-alpha ]quinoxalin-1-one; 1 muM), or methylene blue (MB; 10 muM).3 Elevation of intracellular cyclic GMP accompanying 30 muM Cys-NO addition in non-labouring tissue (7.5 fold) or in labouring tissues (2.5 fold) was completely blocked in tissues that had been pre-treated with ODQ or MB.4 Charybdotoxin (ChTx), iberiotoxin (IbTx) and kaliotoxin (KalTx) all shifted the Cys-NO inhibition curve to the right and reduced the degree of relaxation produced by maximal Cys-NO treatment (100 muM in non-labouring tissue; in labouring tissue, KalTx prevented Cys-NO mediated relaxation in both stimulated and unstimulated tissue.5 Addition of the NO-donor S-nitroso N-acetyl penicillamine (SNAP) produced a dose-dependent relaxation of pregnant myometrium while 3-morpholinosyndonimine (SIN-1) did not. The failure of SIN-1 to relax OT-induced contractions was not due to a failure of the donor to stimulate myometrial GC.6 We demonstrate that despite the ability of NO to stimulate myometrial GC in pregnant uterine muscle, relaxations are independent of cyclic GMP action. Effects of K+-channel inhibitors suggests that NO-induced relaxation in human uterine smooth muscle may be subserved by direct or indirect activation of one or more calcium-activated K+-channels.