Cyclic GMP is a second messenger by which nitric oxide inhibits diaphragm contraction
Cyclic GMP is a second messenger by which nitric oxide inhibits diaphragm contraction
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DOI：
10.1016/s1095-6433(97)00421-2
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发表时间：
1998-01-01
影响因子：
2.3
通讯作者：
Stamler, JS
中科院分区：
文献类型：
--
作者：
Abraham, RZ;Kobzik, L;Stamler, JS
我们已经证明了内源性氮氧化物(NO_2)调节了横隔膜的兴奋收缩偶联。由于环GMP(CGMP)是一氧化氮(NO)抑制血管收缩的第二信使，我们验证了NO通过cGMP在隔膜发挥作用的假说。对大鼠横隔膜的纤维束进行了体外研究。使用cGMP特异性单抗的免疫组织化学分析证实cGMP存在于肌膜下区域，靠近一氧化氮合酶(NOS)。NO供体S-亚硝基-N-乙酰半胱氨酸1 mM(0.55+/-0.05；N=6；P<；0.001)可显著提高对照组肌肉中cGMP的含量(0.27pmol/mg+/-0.01SE)。收缩研究表明，一氧化氮合酶抑制剂N-硝基-L-精氨酸(L-NNA)10 mM使次极大(40 Hz)强直力增加(P<；0.0001)。鸟苷环化酶抑制剂LY83583 5-10 mU M使L-NNA效应增强，40赫兹的作用力增加(P<；0.001)。8-溴-cGMP 1 mM(8-溴-cGMP；细胞透性cGMP类似物；P<；0.0001)或双嘧达莫10 mU M IDPM(磷酸二酯酶抑制剂；P<；0.0001)可部分逆转8-溴-cGMP-NNA的作用。8-Br-GMP和DPM联合应用对L-NNA的逆转作用更为完全(P<；0.0001)。我们得出结论，cGMP作为第二信使发挥作用，NO通过该信使抑制横隔膜收缩。《生物化学物理》119a；1：177-183,1998。(C)1998年爱思唯尔科学公司。
We have shown that endogenous nitrogen oxides (NO,) modulate excitation contraction coupling in diaphragm. Because cyclic GMP (cGMP) is a second messenger for nitric oxide (NO) inhibition of smooth muscle contraction, we tested the hypothesis that NO acts via cGMP in diaphragm. Fiber bundles from rat diaphragm were studied in vitro. Immunohistochemical analysis using a cGMP-specific monoclonal antibody confirmed the presence of cGMP in the subsarcolemmal region, near nitric oxide synthase (NOS). cGMP measured by ELISA in control muscle (0.27 pmol/mg +/- 0.01 SE) was significantly increased by the NO donor S-nitroso-N-acetylcysteine 1 mM (0.55 +/- 0.05; N = 6; P < 0.001). Contractile studies showed that the nitric oxide synthase inhibitor N-nitro-L-arginine (L-NNA) 10 mM increased submaximal (40 Hz) tetanic force (P < 0.0001). L-NNA effects were exaggerated by the guanylate cyclase inhibitor LY83583 5-10 mu M; force at 40 Hz was increased (P < 0.001). L-NNA effects were partially reversed by 8-bromo-cGMP 1 mM (8-Br-GMP; a cell-permeable cGMP analogue; P < 0.0001) or dipyridamole 10 mu M IDPM; a phosphodiesterase inhibitor; P < 0.0001). 8-Br-GMP and DPM produced more-complete L-NNA reversal in combination (P < 0.0001). We conclude that cGMP functions as a second messenger by which NO inhibits diaphragm contraction. COMP BIOCHEM PHYSIOL 119A;1:177-183, 1998. (C) 1998 Elsevier Science Inc.