Bradley K K, Buxton I L, Barber J E, McGaw T, Bradley M E
Department of Pharmacology, University of Nevada, Reno, Nevada 89557, USA.
Am J Physiol. 1998 Dec;275(6):C1668-73. doi: 10.1152/ajpcell.1998.275.6.C1668.
The role of intracellular guanosine 3',5'-cyclic monophosphate concentration ([cGMP]i) in nitric oxide (NO)-mediated relaxations in the uterus has become controversial. We found the NO donor S-nitroso-L-cysteine (CysNO) to potently (IC50 = 30 nM) inhibit spontaneous contractions in the nonpregnant human myometrium. CysNO treatment increased [cGMP]i significantly (P < 0.001), and this increase was blocked by the guanylyl cyclase inhibitors methylene blue (10 microM) or LY-83583 (1 microM); however, pretreatment with these guanylyl cyclase inhibitors failed to block CysNO-mediated relaxations. Intracellular cAMP concentrations were not altered by treatment of tissues with 10 microM CysNO. Incubation with the cGMP analogs 8-bromo-cGMP or beta-phenyl-1,N2-etheno-cGMP did not significantly affect spontaneous contractility. Pretreatment of tissues with charybdotoxin [a calcium-dependent potassium channel (BK) blocker] completely reversed CysNO-induced relaxations. We conclude that NO is a potent inhibitor of spontaneous contractile activity in the nonpregnant human uterus and that, although guanylyl cyclase and BK activities are increased by NO, increases in [cGMP]i are not required for NO-induced relaxations in this tissue.
细胞内3',5'-环磷酸鸟苷浓度（[cGMP]i）在一氧化氮（NO）介导的子宫舒张中的作用已成为一个有争议的问题。我们发现NO供体S-亚硝基-L-半胱氨酸（CysNO）能有效（IC50 = 30 nM）抑制未孕人类子宫肌层的自发收缩。CysNO处理显著增加了[cGMP]i（P < 0.001），并且这种增加被鸟苷酸环化酶抑制剂亚甲蓝（10 microM）或LY-83583（1 microM）阻断；然而，用这些鸟苷酸环化酶抑制剂预处理未能阻断CysNO介导的舒张。用10 microM CysNO处理组织不会改变细胞内cAMP浓度。用cGMP类似物8-溴-cGMP或β-苯基-1,N2-乙烯基-cGMP孵育不会显著影响自发收缩性。用章鱼毒素[一种钙依赖性钾通道（BK）阻滞剂]预处理组织可完全逆转CysNO诱导的舒张。我们得出结论，NO是未孕人类子宫自发收缩活动的有效抑制剂，并且，尽管NO可增加鸟苷酸环化酶和BK活性，但该组织中NO诱导的舒张并不需要[cGMP]i增加。
