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首页> 外文期刊>The European Journal of Neuroscience >RFa-related peptides are algogenic: evidence in vitro and in vivo.
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RFa-related peptides are algogenic: evidence in vitro and in vivo.

机译:与RFa相关的肽具有促生性:体外和体内的证据。

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Abstract RFamide (RFa)-related peptides modulate pain processing in the mammalian CNS. The effects of these peptides are generally considered as 'anti-opioid'. They also decrease the rate of desensitization of acid-sensing ionic channels (ASICs), putative nociceptors in dorsal root ganglia neurons [C. Askwith et al. (2000) Neuron, 26, 133-141]. We have tested the role of mollusc-derived peptide, FMRFa (Phe-Met-Arg-Phe-amide) and its synthetic analogues in peripheral nociception. Here we demonstrate that RFa-related peptides powerfully excite the majority of C-fibres in the skin-nerve preparation of rat: 76% of 55 tested fibres with the conduction velocity below 2 m/s responded with long-lasting discharges to the application of peptides (20 micro m). When injected subcutaneously in vivo (mice), they initiate nociceptive behaviour. We confirm the data on humans [S. Ugawa et al. (2002) J. Clin. Invest., 110, 1185-1190]: the activation of C-fibres by acid is inhibited by channel blocker of ASICs, amiloride. However, there is no correlation in the sensitivity of C-fibres to RFa peptides, protons and amiloride: 74% of tested RFa-sensitive C-fibres were insensitive to protons and in 67% of cases the response to peptides was insensitive to amiloride. Thus, powerful excitatory/algogenic action of RFa-related peptides cannot be interpreted solely in terms of their interaction with ASICs. The peptides do not activate any conductance in the somatic membrane of dorsal root ganglion neurons of rats and probably affect still unidentified molecular target(s) responsible for nociceptive signalling.
机译:摘要RFamide(RFa)相关肽可调节哺乳动物CNS中的疼痛过程。这些肽的作用通常被认为是“抗阿片样物质”。它们还降低了背根神经节神经元中假定的伤害感受器酸敏感离子通道(ASICs)的脱敏率[C. Askwith等。 (2000)Neuron,26,133-141]。我们已经测试了软体动物衍生肽FMRFa(Phe-Met-Arg-Phe-amide)及其合成类似物在周围伤害感受中的作用。在这里,我们证明,与RFa相关的肽可强有力地激发大鼠皮肤神经制剂中的大多数C纤维:55条经测试的纤维中的76%的传导速度低于2 m / s,对长效放电产生了响应。肽(20微米)。当在体内皮下注射(小鼠)时,它们会引发伤害性行为。我们确认有关人类的数据[S.宇川等。 (2002)J.Clin。 [Invest。,110,1185-1190]:ASIC的通道阻滞剂阿米洛利抑制了酸对C纤维的活化。但是,C纤维对RFa肽,质子和阿米洛利的敏感性之间没有相关性:测试的RFa敏​​感C纤维中有74%对质子不敏感,在67%的情况下,对肽的反应对阿米洛利不敏感。因此,不能仅根据它们与ASIC的相互作用来解释RFa相关肽的强大的兴奋/诱变作用。所述肽不激活大鼠背根神经节神经元的体细胞膜中的任何电导,并且可能影响尚未确定的负责伤害性信号传导的分子靶标。

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