Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou, China.
Peptides. 2010 Jan;31(1):94-100. doi: 10.1016/j.peptides.2009.10.013. Epub 2009 Oct 23.
Endokinins are novel tachykinins encoded on the human TAC4 and consist of Endokinin A (EKA), B (EKB), C (EKC) and D (EKD). To date, the function of Endokinins in pain processing was not fully understood. Therefore the aim of this study was to investigate the effects of Endokinin A/B (EKA/B, the common C-terminal decapeptide in EKA and EKB) and Endokinin C/D (EKC/D, the common C-terminal duodecapeptide in EKC and EKD) on pain modulation at supraspinal level in mice. Intracerebroventricular (i.c.v.) administration of EKA/B (1, 3, 12, 20nmol/mouse) dose dependently induced potent analgesic effect. This effect could be fully antagonized by SR140333B but not SR48968C or SR142801. Naloxone could also block the analgesic effect, suggesting that this analgesic effect is related to opioid receptors. However, i.c.v. administration of EKA/B (10, 30, 100pmol/mouse) caused hyperalgesic effect significantly, with a "U" shape curve. Interestingly, the hyperalgesic effect induced by EKA/B could be attenuated by SR140333B, SR142801 but not SR48968C. I.c.v. administration of EKC/D (1, 3, 12, 20nmol/mouse) also dose dependently induced analgesic effect, which could not be blocked by SR48968C or SR142801 or naloxone. But to our astonishment, it could be significantly enhanced by SR140333B. More interestingly, the hyperalgesic effect induced by EKA/B could be significantly attenuated by EKC/D. In addition, the analgesic effect induced by co-administration of EKA/B and EKC/D was much less stronger than the effect of either EKA/B or EKC/D.
内源性神经激肽是一种新型的速激肽，编码于人 TAC4 基因，包括内源性神经激肽 A（EKA）、B（EKB）、C（EKC）和 D（EKD）。迄今为止，内源性神经激肽在疼痛处理中的作用尚未完全阐明。因此，本研究旨在探讨内源性神经激肽 A/B（EKA/B，EKA 和 EKB 的共同 C 端十肽）和内源性神经激肽 C/D（EKC/D，EKC 和 EKD 的共同 C 端十二肽）对小鼠脊髓以上水平疼痛调节的影响。脑室内（i.c.v.）给予 EKA/B（1、3、12、20nmol/只）剂量依赖性地诱导出强烈的镇痛作用。这种作用可以被 SR140333B 完全拮抗，但不能被 SR48968C 或 SR142801 拮抗。纳洛酮也能阻断镇痛作用，提示这种镇痛作用与阿片受体有关。然而，脑室内给予 EKA/B（10、30、100pmol/只）时，明显引起痛觉过敏作用，呈“U”形曲线。有趣的是，EKA/B 引起的痛觉过敏作用可以被 SR140333B、SR142801 而不是 SR48968C 减弱。脑室内给予 EKC/D（1、3、12、20nmol/只）也剂量依赖性地诱导出镇痛作用，不能被 SR48968C 或 SR142801 或纳洛酮阻断。但令我们惊讶的是，它可以被 SR140333B 显著增强。更有趣的是，EKA/B 引起的痛觉过敏作用可以被 EKC/D 显著减弱。此外，EKA/B 和 EKC/D 联合给药诱导的镇痛作用比 EKA/B 或 EKC/D 单独给药的作用弱得多。
