Naono Rumi, Nakayama Tomohiro, Ikeda Tetsuya, Matsushima Osamu, Nishimori Toshikazu
Division of Neurobiology, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan.
Brain Res. 2007 Aug 24;1165:71-80. doi: 10.1016/j.brainres.2007.05.062. Epub 2007 Jul 3.
Endokinins are tachykinin peptides designated from a human preprotachykinin C (PPT-C, TAC4) gene and consist of endokinin A (EKA), endokinin B (EKB), endokinin C (EKC) and endokinin D (EKD). A representative of mammalian tachykinins is substance P (SP), which functions as a neurotransmitter or modulator in the pain system; however, little is known about the role of these endokinins, especially EKC and EKD, in pain processing. Therefore, we evaluated the effects of EKC/D (using the common carboxyl-terminal duodecapeptide in EKC and EKD) on pain processing in rats. Pretreatment with EKC/D prevented induction of scratching behavior and thermal hyperalgesia by intrathecal administration of EKA/B (using the common C-terminal decapeptide in EKA and EKB) and SP and c-Fos expression in laminae I/II and V/VI of the spinal cord by noxious thermal stimulation. A prominent difference between EKC/D and SP is the presence of leucine instead of methionine at the carboxyl-terminal of EKC/D. Thus, to clarify whether leucine at the carboxyl-terminal of EKC/D plays an important role in determining the inhibitory effect of this peptide, we intrathecally administered [Met(12)]-EKC/D in which only leucine of EKC/D is replaced by methionine. This peptide did not exhibit the inhibitory effect on SP-induced scratching behavior or thermal hyperalgesia but conversely caused thermal hyperalgesia. Taken together, these findings indicate that EKC/D has an inhibitory effect on pain processing in the rat spinal cord, and the effect is due to leucine at the carboxyl-terminal of EKC/D.
内激肽是从人类前速激肽原C（PPT-C，TAC4）基因中命名的速激肽肽类，由内激肽A（EKA）、内激肽B（EKB）、内激肽C（EKC）和内激肽D（EKD）组成。哺乳动物速激肽的一个代表是P物质（SP），它在疼痛系统中作为神经递质或调节剂发挥作用；然而，关于这些内激肽，尤其是EKC和EKD在疼痛处理中的作用知之甚少。因此，我们评估了EKC/D（使用EKC和EKD中常见的羧基末端十二肽）对大鼠疼痛处理的影响。EKC/D预处理可预防鞘内注射EKA/B（使用EKA和EKB中常见的C末端十肽）和SP诱导的搔抓行为和热痛觉过敏，以及有害热刺激引起的脊髓I/II层和V/VI层中的c-Fos表达。EKC/D和SP之间的一个显著差异是EKC/D的羧基末端存在亮氨酸而非甲硫氨酸。因此，为了阐明EKC/D羧基末端的亮氨酸在确定该肽的抑制作用中是否起重要作用，我们鞘内注射了[Met(12)]-EKC/D，其中EKC/D中只有亮氨酸被甲硫氨酸取代。该肽对SP诱导的搔抓行为或热痛觉过敏没有表现出抑制作用，反而引起了热痛觉过敏。综上所述，这些发现表明EKC/D对大鼠脊髓的疼痛处理具有抑制作用，且该作用归因于EKC/D羧基末端的亮氨酸。
