Expression of melanocortin receptors and pro-opiomelanocortin in the rat spinal cord in relation to neurotrophic effects of melanocortins

Although neurotrophic effects of alpha-melanocyte-stimulating hormone (alph a-MSH) are well established, the mechanism underlying these effects is unkn own. To identify candidate components of the signaling system that may medi ate these effects, in the present study rat spinal cord, dorsal root gangli a, sciatic nerve and soleus muscle were analysed for the expression of the neural MC3, MC4 and MC5 receptors and for the expression of the melanocorti n precursor pro-opiomelanocortin (POMC). In rat lumbar spinal cord, the MC4 receptor was the only MC receptor subtype for which mRNA was detectable us ing RNAse protection assays. In situ binding studies using I-125-NDP-MSH, a synthetic alpha-MSH analogue, demonstrated MC receptor protein in the rat spinal cord, predominantly localised in substantia gelatinosa and area X, s urrounding the central canal. Furthermore, POMC mRNA was demonstrated in ra t spinal cord and dorsal root ganglia. These findings suggest a functional melanocortin system in the rat spinal cord, that might be involved in perip heral nerve repair. Regulation of POMC or MC receptor transcripts does not appear to be involved in the response to peripheral nerve crush in rats, si nce no change in mRNA expression patterns was detected after sciatic nerve crush, using quantitative RNAse protection assays. Nevertheless, subtle cha nges in melanocortin receptor binding did occur postsurgically in several r egions of the spinal cord in both sham-operated and sciatic nerve-lesioned rats. The robust expression of MC receptor protein in spinal cord regions t hat are generally associated with nociception suggests a potentially broade r 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. (C) 1999 Elsevier Science B.V. All rights reserved.