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首页> 外文期刊>Life sciences >Sodium ions and GTP decrease the potency of (Nphe1)N/OFQ(1-13)NH2 in blocking nociceptin/orphanin FQ receptors coupled to cyclic AMP in N1E-115 neuroblastoma cells and rat olfactory bulb.
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Sodium ions and GTP decrease the potency of (Nphe1)N/OFQ(1-13)NH2 in blocking nociceptin/orphanin FQ receptors coupled to cyclic AMP in N1E-115 neuroblastoma cells and rat olfactory bulb.

机译：钠离子和GTP会降低（Nphe1）N / OFQ（1-13）NH2在阻断N1E-115神经母细胞瘤细胞和大鼠嗅球中与环AMP偶联的伤害感受肽/ orphanin FQ受体的能力。

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The pseudopeptide [Nphe(1)]N/OFQ(1-13)NH(2) (Nphe) has been shown to act as a pure, selective and competitive antagonist of nociceptin/orphanin FQ (N/OFQ) receptors in different tissues. However, Nphe displayed a highly variable potency, with pA(2) values ranging from 5.96 to 8.45. In the present study, we show that sodium ions and GTP markedly affect the potency of Nphe in blocking N/OFQ receptors coupled to cyclic AMP inhibition in different cellular systems. In intact N1E-115 neuroblastoma cells, the pA(2) value of Nphe increased from 7.13 to 8.02 when the extracellular sodium concentration was reduced from 138 to 2.5 mM. When N/OFQ inhibition of adenylyl cyclase activity was assayed in cell membranes, 100 mM NaCl decreased the pK(i) value of Nphe from 8.38 to 7.32, but increased that of the nonpeptide N/OFQ receptor antagonist CompB from 8.61 to 8.92. Similar effects of sodium ions on the potencies of Nphe and CompB were observed when the compounds were used to antagonize the N/OFQ inhibition of adenylyl cyclase activity in membranes of the external plexiform layer of the rat olfactory bulb. In the same assay, the increase of GTP concentration from 0.1 to 200 micro M decreased Nphe potency by 8-fold. These data demonstrate that sodium ions and GTP affect the potency of Nphe in a manner similar to that of agonists but not of pure antagonists and suggest that these factors may contribute to the reported variability of Nphe affinity constant.
机译：伪肽[Nphe（1）] N / OFQ（1-13）NH（2）（Nphe）已显示出在不同组织中可作为痛敏肽/孤儿蛋白FQ（N / OFQ）受体的纯，选择性和竞争性拮抗剂。但是，Nphe显示了高度可变的效价，pA（2）值的范围为5.96至8.45。在本研究中，我们表明钠离子和GTP显着影响Nphe在阻断N / OFQ受体与环状AMP抑制耦合在不同细胞系统中的效力。在完整的N1E-115神经母细胞瘤细胞中，当细胞外钠浓度从138 mM降低到2.5 mM时，Nphe的pA（2）值从7.13增加到8.02。当在细胞膜中检测到N / OFQ对腺苷酸环化酶活性的抑制作用时，100 mM NaCl将Nphe的pK（i）值从8.38降低到7.32，但将非肽N / OFQ受体拮抗剂CompB的pK（i）值从8.61增加到8.92。当使用该化合物拮抗N / OFQ抑制大鼠嗅球外丛状膜中腺苷酸环化酶活性时，观察到钠离子对Nphe和CompB效力的相似影响。在同一试验中，GTP浓度从0.1到200 micro M的增加将Nphe效能降低了8倍。这些数据表明钠离子和GTP以类似于激动剂的方式影响Nphe的效力，但不影响纯拮抗剂的效力，并表明这些因素可能有助于Nphe亲和常数的可变性。

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