Endogenous nitric oxide suppresses rat myometrial connexin 43 gap junction protein expression during pregnancy.
Endogenous nitric oxide suppresses rat myometrial connexin 43 gap junction protein expression during pregnancy.
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DOI：
10.1095/biolreprod61.1.8
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发表时间：
1999-07
影响因子：
3.6
通讯作者：
S. Sladek;Andrea Westerhausen-Larson;James M. Roberts
中科院分区：
文献类型：
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作者：
S. Sladek;Andrea Westerhausen-Larson;James M. Roberts
一氧化氮（NO）合成酶（NOS）在妊娠子宫中具有活性，其活性在分娩前降低。我们测试了NO通过抑制分娩所需基因的表达来帮助维持子宫静止的假设。用诱导型NOS （iNOS）抑制剂n -亚氨基乙基-赖氨酸（NIL）或内皮型NOS抑制剂硝基-l -精氨酸甲酯（L-NAME）处理妊娠大鼠（妊娠18 d）；24h后，用免疫印迹法检测子宫肌瘤连接蛋白43 （Cx43）蛋白，用Northern分析法检测mRNA。采用放射配体结合法检测子宫内膜催产素受体（OTR）水平，免疫印迹法检测前列腺素H合成酶（PGHS）蛋白水平。NOS活性测定证实子宫NOS阻断。我们发现，在妊娠19天而不是17天时，NIL而不是L-NAME显著地将子宫肌瘤Cx43蛋白增加到分娩水平。在24 h时，稳态mRNA浓度没有变化。NOS抑制没有增加OTR或PGHS蛋白的浓度，也没有降低母体血清黄体酮。我们得出结论，内源性子宫NO通过iNOS抑制妊娠大鼠子宫内膜Cx43间隙连接蛋白的表达。虽然确切的机制尚不清楚，但由于抑制松弛而增加的子宫壁拉伸可能解释了Cx43基因转录的增加。
Nitric oxide (NO) synthase (NOS) is active in the gravid uterus, and its activity decreases prior to the onset of parturition. We tested the hypothesis that NO helps maintain uterine quiescence by suppressing the expression of genes necessary for parturition. Pregnant rats (18 days gestation) were treated with inducible NOS (iNOS) inhibitor N-iminoethyl-L-lysine (NIL) or endothelial NOS inhibitor nitro-L-arginine methyl ester (L-NAME); 24 h later, uteri were analyzed for myometrial connexin 43 (Cx43) protein by immunoblotting and mRNA by Northern analysis. Myometrial oxytocin receptors (OTR) were measured by radioligand binding, and decidual prostaglandin H synthase (PGHS) protein by immunoblotting. Uterine NOS blockade was verified by NOS activity assay. We found that NIL, but not L-NAME, significantly increased myometrial Cx43 protein to parturitional levels with treatment at 19 but not 17 days gestation. Steady state mRNA concentrations were not changed at 24 h. NOS inhibition did not increase the concentrations of OTR, or PGHS protein, nor did it decrease maternal serum progesterone. We conclude that endogenous uterine NO from iNOS suppresses myometrial Cx43 gap junction protein expression during rat pregnancy. Although the exact mechanism is unknown, an increase of uterine wall stretch due to inhibition of relaxation could account for increased Cx43 gene transcription.