Gouardères Christine, Kieffer Brigitte L, Zajac Jean-Marie
Institut de Pharmacologie et de Biologie Structurale, C.N.R.S. UMR 5089, 205 Route de Narbonne, 31077 Toulouse Cedex, France.
J Chem Neuroanat. 2004 May;27(2):119-28. doi: 10.1016/j.jchemneu.2004.01.002.
Mice lacking the mu-delta-kappa-opioid receptor (MOR/DOR/KOR) genes and their corresponding wild-type littermates have been used to quantify NPFF(1) and NPFF(2) (neuropeptide FF) receptors by in vitro autoradiography in the central nervous tissues. Adjacent coronal sections were labelled with [125I]YVP ([125I]YVPNLPQRF-NH(2)) and [125I]EYF ([125I]EYWSLAAPQRF-NH(2)) as specific radioligands for NPFF(1) and NPFF(2) receptors, respectively. NPFF(2) receptors are predominantly expressed in both genotypes, but their density increases significantly in non cortical regions of mutant mice: 64% in the amygdaloid area, 89, 308, 1214 and 49% in the nucleus of the vertical limb of the diagonal band, substantia nigra, the vestibular nucleus and the spinal cord, respectively. In contrast, the density of the NPFF(1) subtype is lower than NPFF(2) in both genotypes and significantly decreased in some brain areas of mutant mice: -99, -90 and -90% in the nucleus of the vertical limb of the diagonal band, substantia nigra and the spinal cord, respectively. This study shows that mice lacking opioid receptors have brain region-dependent increases (NPFF(2)) and decreases (NPFF(1)) in NPFF receptors densities and suggests a different functional participation of each NPFF receptor subtype in the actions of opioids.
缺乏μ-δ-κ阿片受体（MOR/DOR/KOR）基因的小鼠及其相应的野生型同窝仔鼠已被用于通过体外放射自显影法对中枢神经组织中的NPFF(1)和NPFF(2)（神经肽FF）受体进行定量。相邻的冠状切片分别用[125I]YVP（[125I]YVPNLPQRF-NH(2)）和[125I]EYF（[125I]EYWSLAAPQRF-NH(2)）标记，作为NPFF(1)和NPFF(2)受体的特异性放射性配体。NPFF(2)受体在两种基因型中均有主要表达，但在突变小鼠的非皮质区域其密度显著增加：在杏仁核区域增加64%，在斜角带垂直支核、黑质、前庭核和脊髓中分别增加89%、308%、1214%和49%。相比之下，NPFF(1)亚型的密度在两种基因型中均低于NPFF(2)，且在突变小鼠的一些脑区显著降低：在斜角带垂直支核、黑质和脊髓中分别降低-99%、-90%和-90%。本研究表明，缺乏阿片受体的小鼠脑区中NPFF受体密度存在脑区依赖性增加（NPFF(2)）和降低（NPFF(1)），提示每种NPFF受体亚型在阿片类药物作用中具有不同的功能参与。
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