van der Kraan M, Tatro J B, Entwistle M L, Brakkee J H, Burbach J P, Adan R A, Gispen W H
Rudolf Magnus Institute for Neurosciences, Department of Medical Pharmacology, Utrecht University, Universiteitsweg 100, 3584 CG, Utrecht, Netherlands.
Brain Res Mol Brain Res. 1999 Jan 8;63(2):276-86. doi: 10.1016/s0169-328x(98)00291-5.
Although neurotrophic effects of alpha-melanocyte-stimulating hormone (alpha-MSH) are well established, the mechanism underlying these effects is unknown. To identify candidate components of the signaling system that may mediate these effects, in the present study rat spinal cord, dorsal root ganglia, sciatic nerve and soleus muscle were analysed for the expression of the neural MC3, MC4 and MC5 receptors and for the expression of the melanocortin precursor pro-opiomelanocortin (POMC). In rat lumbar spinal cord, the MC4 receptor was the only MC receptor subtype for which mRNA was detectable using RNAse protection assays. In situ binding studies using 125I-NDP-MSH, a synthetic alpha-MSH analogue, demonstrated MC receptor protein in the rat spinal cord, predominantly localised in substantia gelatinosa and area X, surrounding the central canal. Furthermore, POMC mRNA was demonstrated in rat spinal cord and dorsal root ganglia. These findings suggest a functional melanocortin system in the rat spinal cord, that might be involved in peripheral nerve repair. Regulation of POMC or MC receptor transcripts does not appear to be involved in the response to peripheral nerve crush in rats, since no change in mRNA expression patterns was detected after sciatic nerve crush, using quantitative RNAse protection assays. Nevertheless, subtle changes in melanocortin receptor binding did occur postsurgically in several regions of the spinal cord in both sham-operated and sciatic nerve-lesioned rats. The robust expression of MC receptor protein in spinal cord regions that are generally associated with nociception suggests a potentially broader involvement of endogenous melanocortins in spinal pathways which mediate the responses to peripheral injury, in addition to any direct melanocortin effects on sprouting and neurite outgrowth.
尽管α-黑素细胞刺激素（α-MSH）的神经营养作用已得到充分证实，但其作用机制尚不清楚。为了确定可能介导这些作用的信号系统的候选成分，在本研究中，对大鼠脊髓、背根神经节、坐骨神经和比目鱼肌进行了分析，以检测神经MC3、MC4和MC5受体的表达以及黑皮质素前体阿片促黑素皮质素原（POMC）的表达。在大鼠腰段脊髓中，MC4受体是唯一可通过核糖核酸酶保护试验检测到mRNA的MC受体亚型。使用合成的α-MSH类似物125I-NDP-MSH进行的原位结合研究表明，大鼠脊髓中存在MC受体蛋白，主要定位于中央管周围的胶状质和X区。此外，在大鼠脊髓和背根神经节中也证实了POMC mRNA的存在。这些发现提示大鼠脊髓中存在一个功能性黑皮质素系统，可能参与周围神经修复。POMC或MC受体转录本的调节似乎与大鼠周围神经挤压反应无关，因为在坐骨神经挤压后，使用定量核糖核酸酶保护试验未检测到mRNA表达模式的变化。然而，在假手术和坐骨神经损伤的大鼠中，脊髓的几个区域在手术后确实发生了黑皮质素受体结合的细微变化。MC受体蛋白在通常与伤害感受相关的脊髓区域的强烈表达表明，除了黑皮质素对发芽和神经突生长的任何直接作用外，内源性黑皮质素可能在介导对周围损伤反应的脊髓通路中具有更广泛的参与。
