Hence, the capacity of this peptide to bind PACAP receptors and protect neuroblastoma cells was evaluated under conditions of mitochondrial dysfunction and glutamate excitotoxicity.
The immediate early response gene FOS is a well-known marker of neuronal activation, so we used a human neuroblastoma cell line NB-1 to explore the role of calmodulin in PACAP-induced FOS gene expression.
In addition, PACAP and its receptors have been described in neuroblastoma and pheochromocytoma, and the neuropeptide regulates the differentiation and activity of sympathoadrenal-derived tumoral cell lines, suggestive of an important role in the pathophysiology of the sympathoadrenal lineage.
These results provide evidence that the neurotrophic effects of PACAP-38 on human SH-SY5Y neuroblastoma cells are mediated by the PAC(1) receptor through a cAMP-dependent but PKA-independent mechanism, and furthermore suggest that this involves Epac-dependent activation of ERK as well as activation of the p38 MAP kinase signaling pathway.
In the human neuroblastoma NB-OK-1 cell line, [(3)H] thymidine incorporation was increased in response to ANP, decreased in response to pituitary adenylate cyclase-activating polypeptide (PACAP-27), and the stimulatory effect of ANP was inhibited by PACAP-27.