Dissociation of pharmacological pro- and anti-opioid effects by neuropeptide FF analogs.
Dissociation of pharmacological pro- and anti-opioid effects by neuropeptide FF analogs.
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DOI：
10.1016/s0014-2999(02)01983-0
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发表时间：
2002-08
影响因子：
5
通讯作者：
I. Quelven;A. Roussin;O. Burlet-Schiltz;C. Gouardères;J. Tafani;H. Mazarguil;J. Zajac
中科院分区：
文献类型：
--
作者：
I. Quelven;A. Roussin;O. Burlet-Schiltz;C. Gouardères;J. Tafani;H. Mazarguil;J. Zajac
神经肽FF（NPFF）及其类似物1DMe（[D-Tyr 1，（NMe）Phe 3]NPFF）可逆转或增强吗啡镇痛作用。在小鼠甩尾试验中，研究了1DMe及其相关化合物Nic-1DMe（烟碱酰-Pro-1DMe）在局部（i. c. v.和i.t.）和系统管理。尽管Nic-1DMe和1DMe对NPFF 1和NPFF 2受体表现出相同的亲和力和选择性，但与1DMe相反，Nic-1DMe在i. c. v.和i. p.给药后不能抑制吗啡诱导的镇痛作用。相反，在i.t.和i. p.给药，两种神经肽FF类似物都能增强吗啡镇痛。1DMe和Nic-1DMe之间的处置参数的差异是有证据的，这表明两种神经肽FF类似物可以刺激差异脊髓上神经肽FF受体。Nic-1DMe对脊髓神经元通路的主要激活可以解释该化合物在i.t.后的选择性前阿片样物质作用，i. c. v.和i. p.给药。
Neuropeptide FF (NPFF) and its analog 1DMe ([D-Tyr1,(NMe)Phe3]NPFF) have been shown to reverse or potentiate morphine analgesia in rat depending on the supraspinal or spinal site of injection. The properties, in the mouse tail-flick test, of 1DMe and its related compound Nic-1DMe (Nicotinoyl-Pro-1DMe) were investigated after their local (i.c.v. and i.t.) and systemic administration. Whereas Nic-1DMe and 1DMe exhibit the same affinity and selectivity towards NPFF1and NPFF2receptors, Nic-1DMe, in contrast to 1DMe, is unable to inhibit morphine-induced analgesia after i.c.v. and i.p. administration. Conversely, after i.t. and i.p. administration, both neuropeptide FF analogs could potentiate morphine analgesia. Differences in disposition parameters between 1DMe and Nic-1DMe are evidenced, suggesting that the two neuropeptide FF analogs could stimulate differentially supraspinal neuropeptide FF receptors. The predominant activation of spinal neuronal pathways by Nic-1DMe could explain the selective pro-opioid action of this compound after i.t., i.c.v. and i.p. administration.