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 (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.
van der Kraan
M
M
Rudolf Magnus Institute for Neurosciences, Department of Medical Pharmacology, Utrecht University, Universiteitsweg 100, 3584 CG, Utrecht, Netherlands.
Tatro
J B
JB
Entwistle
M L
ML
Brakkee
J H
JH
Burbach
J P
JP
Adan
R A
RA
Gispen
W H
WH
D000818:Animals; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology*; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D009409:Nerve Crush; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009416:Nerve Regeneration; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D018043:Receptors, Corticotropin / Q000096:biosynthesis*; D044101:Receptors, Melanocortin; D012584:Sciatic Nerve / Q000293:injuries; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D009414:Nerve Growth Factors; D012333:RNA, Messenger; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D011333:Pro-Opiomelanocortin; D009074:Melanocyte-Stimulating Hormones