Rocha-González H I, Castañeda-Corral G, Araiza-Saldaña C I, Ambriz-Tututi M, Caram-Salas N L, Torres-López J E, Murbartián J, Granados-Soto V
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados, Sede Sur, Calz. Tenorios 235, Deleg. Tlalpan, Col. Granjas Coapa, 14330 México, D.F., Mexico.
Neuroscience. 2009 Apr 21;160(1):156-64. doi: 10.1016/j.neuroscience.2009.02.033. Epub 2009 Feb 25.
mRNA and protein presence of Na+/H+ exchanger (NHE) 1 (NHE1) and 5 (NHE5) in dorsal root ganglion (DRG) and dorsal spinal cord as well as its possible role in three inflammatory nociception tests were determined. Local peripheral ipsilateral, but not contralateral, administration of NHE inhibitors 5-(N,N-dimethyl)amiloride hydrochloride (DMA, 0.3-30 microM/paw), 5-(N-ethyl-N-isopropyl)amiloride (EIPA, 0.3-30 microM/paw) and amiloride (0.1-10 microM/paw) significantly increased flinching but not licking behavior in the capsaicin and 5-HT tests. Moreover, DMA and EIPA (0.03-30 microM/paw) as well as amiloride (0.1-1 microM/paw) augmented, in a dose-dependent manner, 0.5% formalin-induced flinching behavior during phase II but not during phase I. Reverse transcription-polymerase chain reaction showed the expression of NHE1 and NHE5 in DRG and dorsal spinal cord. Western blot analysis confirmed the presence of NHE1 in DRG and spinal cord. Moreover, NHE5 was expressed in dorsal spinal cord, but not in DRG where a 45 kDa truncated isoform of NHE5 was identified. Collectively, these data suggest that NHE1, but not NHE5, plays an important role reducing inflammatory pain in rats.
测定了背根神经节(DRG)和脊髓背角中钠氢交换体(NHE)1(NHE1)和5(NHE5)的mRNA和蛋白表达情况,以及它们在三种炎性伤害感受试验中的可能作用。在辣椒素和5-羟色胺试验中,向同侧局部外周(而非对侧)给予NHE抑制剂盐酸5-(N,N-二甲基)阿米洛利(DMA,0.3 - 30微摩尔/爪)、5-(N-乙基-N-异丙基)阿米洛利(EIPA,0.3 - 30微摩尔/爪)和阿米洛利(0.1 - 10微摩尔/爪),显著增加了缩足反应,但未增加舔舐行为。此外,DMA和EIPA(0.03 - 30微摩尔/爪)以及阿米洛利(0.1 - 1微摩尔/爪)以剂量依赖方式增强了0.5%福尔马林诱导的II期缩足行为,但I期未增强。逆转录-聚合酶链反应显示DRG和脊髓背角中有NHE1和NHE5的表达。蛋白质印迹分析证实DRG和脊髓中有NHE1存在。此外,NHE5在脊髓背角表达,但在DRG中未表达,在DRG中鉴定出一种45 kDa的NHE5截短异构体。总体而言,这些数据表明NHE1而非NHE5在减轻大鼠炎性疼痛中起重要作用。