Leucine at the carboxyl-terminal of endokinins C and D contributes to elicitation of the antagonistic effect on substance P in rat pain processing
Leucine at the carboxyl-terminal of endokinins C and D contributes to elicitation of the antagonistic effect on substance P in rat pain processing
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DOI：
10.1016/j.brainres.2007.05.062
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发表时间：
2007-08-24
期刊：
影响因子：
2.9
通讯作者：
Nishimori, Toshikazu
中科院分区：
文献类型：
--
作者：
Naona, Rumi;Nakayama, Tomohiro;Nishimori, Toshikazu
内啡肽（Endokinins）是一种由人前内啡肽C （pt -C, TAC4）基因指定的快激肽，由内啡肽a （EKA）、内啡肽B （EKB）、内啡肽C （EKC）和内啡肽D （EKD）组成。哺乳动物速激素的代表是P物质（SP），它在疼痛系统中起神经递质或调节剂的作用；然而，对于这些内啡肽，特别是EKC和EKD在疼痛加工中的作用知之甚少。因此，我们评估了EKC/D（利用EKC和EKD中共同的羧基末端十二肽）对大鼠疼痛加工的影响。EKC/D预处理可以通过鞘内给药EKA/B（使用EKA和EKB中常见的c端十肽）和脊髓I/II和V/VI层中SP和c-Fos的表达来预防搔抓行为和热痛觉过敏。EKC/D与SP的一个显著区别是在EKC/D的羧基端存在亮氨酸而不是蛋氨酸。因此，为了阐明EKC/D羧基末端的亮氨酸是否在决定该肽的抑制作用中起重要作用，我们在鞘内给药[Met(12)]-EKC/D，其中EKC/D的亮氨酸仅被蛋氨酸取代。该肽对sp诱导的抓痕行为或热痛觉过敏没有抑制作用，但相反会引起热痛觉过敏。综上所述，EKC/D对大鼠脊髓疼痛加工具有抑制作用，这种抑制作用与EKC/D羧基末端的亮氨酸有关。(c) 2007 Elsevier B.V.版权所有
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. (c) 2007 Elsevier B.V. All rights reserved.