Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Korea.
Korean J Physiol Pharmacol. 2012 Jun;16(3):211-7. doi: 10.4196/kjpp.2012.16.3.211. Epub 2012 Jun 26.
Recent studies have demonstrated that nitric oxide (NO) activates transient receptor potential vanilloid subtype 1 (TRPV1) via S-nitrosylation of the channel protein. NO also modulates various cellular functions via activation of the soluble guanylyl cyclase (sGC)/protein kinase G (PKG) pathway and the direct modification of proteins. Thus, in the present study, we investigated whether NO could indirectly modulate the activity of TRPV1 via a cGMP/PKG-dependent pathway in cultured rat dorsal root ganglion (DRG) neurons. NO donors, sodium nitroprusside (SNP) and S-nitro-N-acetylpenicillamine (SNAP), decreased capsaicin-evoked currents (I(cap)). NO scavengers, hemoglobin and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO), prevented the inhibitory effect of SNP on I(cap). Membrane-permeable cGMP analogs, 8-bromoguanosine 3', 5'-cyclic monophosphate (8bromo-cGMP) and 8-(4chlorophenylthio)-guanosine 3',5'-cyclic monophosphate (8-pCPT-cGMP), and the guanylyl cyclase stimulator YC-1 mimicked the effect of SNP on I(cap). The PKG inhibitor KT5823 prevented the inhibition of I(cap) by SNP. These results suggest that NO can downregulate the function of TRPV1 through activation of the cGMP/PKG pathway in peripheral sensory neurons.
最近的研究表明，一氧化氮（NO）通过通道蛋白的 S-亚硝基化来激活瞬时受体电位香草酸亚型 1（TRPV1）。NO 还通过激活可溶性鸟苷酸环化酶（sGC）/蛋白激酶 G（PKG）途径和直接修饰蛋白质来调节各种细胞功能。因此，在本研究中，我们研究了 NO 是否可以通过培养的大鼠背根神经节（DRG）神经元中的 cGMP/PKG 依赖性途径间接调节 TRPV1 的活性。NO 供体硝普钠（SNP）和 S-亚硝基-N-乙酰青霉胺（SNAP）降低了辣椒素诱导的电流（I（cap））。NO 清除剂血红蛋白和 2-（4-羧基苯基）-4,4,5,5-四甲基咪唑啉-1-氧-3-氧化物（CPTIO）阻止了 SNP 对 I（cap）的抑制作用。膜通透型 cGMP 类似物 8-溴鸟苷 3'，5'-环单磷酸（8bromo-cGMP）和 8-（4-氯苯基硫代）鸟苷 3'，5'-环单磷酸（8-pCPT-cGMP）以及鸟苷酸环化酶刺激剂 YC-1 模拟了 SNP 对 I（cap）的作用。PKG 抑制剂 KT5823 阻止了 SNP 对 I（cap）的抑制作用。这些结果表明，NO 可以通过激活外周感觉神经元中的 cGMP/PKG 途径来下调 TRPV1 的功能。
