Em. Hol et al., THE ROLE OF CALCIUM AND CAMP IN THE MECHANISM OF ACTION OF 2 MELANOCORTINS - ALPHA-MSH AND THE ACTH(4-9) ANALOG ORG-2766, Brain research, 662(1-2), 1994, pp. 109-116
Melanocortins accelerate functional recovery after nerve crush and enh
ance neurite outgrowth in vitro. To get more insight in the mechanism
of action of melanocortins, we studied the effects of two neurotrophic
peptides: alpha-melanocyte-stimulating hormone (alpha MSH) and an adr
enocorticotropin(4-9) analogue Org 2766 on second messengers in cultur
es of spinal cord (SC), dorsal root ganglion (DRG) and Schwann cells.
alpha MSH (10 mu M) enhanced the forskolin-induced cAMP production in
SC-(45%) and in DRG-cells (35%). Org 2766 (1 mu M) induced an increase
in cAMP only in SC-cells (39%). The peptides did not affect the cAMP
levels in Schwann cells. Neither peptide evoked significant changes in
the intracellular free calcium concentration ([Ca2+](i)) in batch-mea
surements of all cell types, however, Ca2+-imaging revealed an infrequ
ent occurrence of large [Ca2+](i)-elevations in individual SC-neurons.
The results indicate that SC- and DRG-cells are targets for both pept
ides, while Schwann cells are not or exploit different pathways. We ob
served for alpha MSH that cAMP production always coincides with outgro
wth stimulation, whereas for Org 2766 cAMP production and outgrowth st
imulation appear not causally related. These differences in second mes
senger stimulation could be explained by receptor heterogeneity. We su
ggest that alpha MSH and Org 2766 act through different receptors, eac
h with its own signalling pathways.