Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Medicine, and Institute of Biochemistry and Molecular Biology, School of Life Sciences, and State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, PR China.
Peptides. 2010 Apr;31(4):683-8. doi: 10.1016/j.peptides.2009.11.003. Epub 2009 Nov 14.
Neuropeptide FF (NPFF) belongs to a neuropeptide family including two precursors (pro-NPFF(A) and pro-NPFF(B)) and two receptors (NPFF(1) and NPFF(2)). NPFF and NPFF receptor mRNAs have been reported to be highly expressed and localized in the rat and human spinal cord. In the present study, the i.t. action of NPFF system on blood pressure and heart rate were examined using NPFF and two related agonists, NPVF and dNPA, which exhibit highest selectivities for NPFF(1) and NPFF(2) receptors, respectively. In urethane-anesthetized rats, NPFF and related peptides (5-40 nmol, i.t.) produced significant pressor and tachycardic responses at the spinal cord level. These effects were dose-dependent and similar with respect to time-course for the three peptides. Furthermore, i.t. injection of RF9 (20 nmol), a selective NPFF antagonist, significantly antagonized the cardiovascular responses to 20 nmol NPFF and related peptides (i.t.). Moreover, pretreatment of the rats with alpha-adrenoceptor antagonist phentolamine (1mg/kg, i.v.) significantly reduced the pressor effects of NPFF. Nevertheless, pretreatment with muscarinic receptor and adrenoceptor antagonists (i.v.) could block the tachycardic effects induced by NPFF. Collectively, our results suggested that i.t. administration of NPFF and related peptides increased MAP and HR which were possibly mediated by the activation of both NPFF(1) and NPFF(2) receptors in the rat spinal cord. In addition, our results showed that the muscarinic receptor and adrenoceptor participated in the tachycardic response to i.t. NPFF, while alpha-adrenoceptor played an important role in the regulation of pressor effect of NPFF.
神经肽 FF（NPFF）属于一种神经肽家族，包括两个前体（pro-NPFF(A)和 pro-NPFF(B)）和两个受体（NPFF(1)和 NPFF(2)）。NPFF 和 NPFF 受体 mRNA 已在大鼠和人体脊髓中报告表达水平高且定位于此。在本研究中，使用 NPFF 和两种相关激动剂，NPVF 和 dNPA，它们分别对 NPFF(1)和 NPFF(2)受体表现出最高的选择性，检查了 NPFF 系统对血压和心率的脊髓内作用。在乌拉坦麻醉的大鼠中，NPFF 和相关肽（5-40nmol，脊髓内）在脊髓水平产生显著的升压和心动过速反应。这些作用呈剂量依赖性，三种肽的时程相似。此外，脊髓内注射选择性 NPFF 拮抗剂 RF9（20nmol）显著拮抗 20nmol NPFF 和相关肽（脊髓内）引起的心血管反应。此外，预先用α-肾上腺素能受体拮抗剂酚妥拉明（1mg/kg，静脉内）预处理大鼠可显著降低 NPFF 的升压作用。然而，用毒蕈碱受体和肾上腺素受体拮抗剂（静脉内）预处理可阻断 NPFF 引起的心动过速作用。总的来说，我们的结果表明，NPFF 和相关肽的脊髓内给药增加了 MAP 和 HR，这可能是由大鼠脊髓中 NPFF(1)和 NPFF(2)受体的激活介导的。此外，我们的结果表明，毒蕈碱受体和肾上腺素受体参与了脊髓内 NPFF 引起的心动过速反应，而α-肾上腺素能受体在 NPFF 升压作用的调节中起重要作用。
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