Pharmacological aspects of the influence of melanocortins on the formation of regenerative peripheral nerve sprouts.
Adrenocorticotropin (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH) stimulate the initial sprouting response in the crushed rat sciatic nerve. In this report a detailed analysis of the neurotrophic action of Org.2766 [a degradation resistant ACTH(4-9) analog] and alpha-MSH is described. Org.2766 treatment results in enhanced numbers of outgrowing sprouts in the damaged nerve. The growth velocity of the sprouts is not affected. The peptide effect is dose-dependent. A single peptide injection administered immediately following the crush stimulates the formation of sprouts significantly. Continued high blood levels of Org.2766 are probably not critical for the neurotrophic effect of these peptides, since a more moderate dosing protocol (injections given every 48 hr) was more effective than more frequent injections (injections given every 12 hr). The present results further the understanding of the mode of action of ACTH/alpha-MSH-like peptides and underscore the necessity to test a wide range of doses and injection protocols to avoid false negative results in clinical work being planned to start in the near future.
Verhaagen
J
J
Edwards
P M
PM
Jennekens
F G
FG
Gispen
W H
WH
D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D005260:Female; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology*; D013979:Tibial Nerve / Q000187:drug effects / Q000502:physiology*
D000927:Anticonvulsants; D010446:Peptide Fragments; C013765:Org 2766; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones