Non-Corticotropic ACTH Peptides Modulate Nerve Development and Regeneration

Abstract

Short peptide sequences of ACTH 1-39 (the ACTH 4-9 analog Org 2766, ACTH 4-10 and its analog BIM 22015, and ACTH 1-13 [alpha-MSH]), which do not stimulate the adrenal cortex, have profound effects on the developing and regenerating neuromuscular system, in neonatal and in adult rats. Both development and regeneration are accelerated, as indicated by improved morphological, electrophysiological, behavioral and biochemical parameters. Regeneration in the central nervous system is problematic but the ACTH peptides may provide protection for CNS neurons, enhance denervation sensitivity or permit compensatory processes which facilitate functional recovery. Neuronal cells in culture respond to ACTH peptides by greater neurite outgrowth, and in some cell types, by increased B-50 expression. In all cases, susceptibility to ACTH peptide treatment varies with cell type, age, the specific peptide administered, its dosage and pattern of administration. External stress and the gender of the animal are additional factors that interact with the neurotrophic actions of the melanocortins.

Melanocortin-4 Receptor Messenger Ribonucleic Acid Expression in Rat Cardiorespiratory, Musculoskeletal, and Integumentary Systems

“…Our study now shows that MC4-R mRNA is also expressed in fetal skeletal muscle, in particular the abdominal wall and limb muscles. Melanocortins accelerate maturation of the neuromuscular system when they are administered during development (22,23). Therefore, there may be a role for the MC4-R in melanocortin-induced myocyte proliferation.…”

Targeting Melanocortin Receptors as a Novel Strategy to Control Inflammation

“…Reproduced from Rajora et al, 1996, with permission. 18 Dekker, 1988;Van der Zee et al, 1988;Strand et al, 1989Strand et al, , 1993Strand et al, , 1994Antonawich et al, 1994;Hol et al, 1994;Laquerriere et al, 1994;Plantinga et al, 1995;van de Meent et al, 1997;Joosten et al, 1999;Lankhorst et al, 1999Lankhorst et al, , 2000van der Kraan et al, 1999). A recent study shows that also melanotan II has potent influences in nerve regeneration and neuroprotection (Ter Laak et al, 2003).…”

ATF/CREB Elements in the Herpes Simplex Virus Type 1 Latency-Associated Transcript Promoter Interact with Members of the ATF/CREB and AP-1 Transcription Factor Families

“…It is possible that the biochemical events involving alterations in CRE-binding activity that we observe in the C1300 cell line using a cAMP analog mimic some of the stress-induced regenerative events that occur in sensory neurons during HSV infection. In support of this hypothesis is the result which shows that a peptide hormone (alpha-melanocyte-stimulating hormone) released from the pituitary gland and keratinocytes following injury and inflammation can elevate intracellular cAMP levels in dorsal root ganglion cells, stimulate neurite outgrowth, and facilitate regeneration of peripheral nerves [34,69]. Further elucidation of the cellular events associated with HSV infection are required to determine the validity of this model.…”