38‐Amino acid form of pituitary adenylate cyclase activating peptide induces process outgrowth in human neuroblastoma cells

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Abstract
Permanent cell lines from human neuroblastoma, a sympathoadrenal malignancy, are known to exhibit a more neuronal phenotype characterized by outgrowth of long processes in response to multiple second messenger analogs. In this report we demonstrate that the 38‐amino acid form of a peptide homologous to vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptide (PACAP), as well as the 27‐amino acid form of PACAP, induce NB‐OK human neuroblastoma cells to extrude cellular processes within 5 hr of treatment with either peptide at 10−8 M. Treatment of NB‐OK cells with PACAP38 or PACAP27 at 10−8 M for 1 hr also elevates cAMP content greater than 100‐fold and inositol lipid turnover 11‐ to 12‐fold. VIP acutely induces process outgrowth and elevates intracellular second messenger levels in NB‐OK cells only at higher concentrations, 10−6 M or greater. In contrast to the equipotency of PACAP27 and PACAP38 in stimulating the outgrowth of processes observed after 5 hr of treatment, PACAP38 is much more potent than PACAP27 when NB‐OK cells are scored for process outgrowth after 72 hr of treatment. Correlating with the extended time course over which morphologic changes are seen with PACAP38, cAMP levels remain elevated for a more prolonged time span during treatment with PACAP38 than PACAP27. After 72 hr of treatment with PACAP38 versus treatment with PACAP27, cAMP levels are elevated 10‐fold versus 3‐fold, respectively. PACAP38 at 10−8 M also induces process outgrowth in two additional human neuroblastoma lines tested, SMS‐KAN and LA‐N‐1, whereas PACAP27 and VIP at the same concentration are less effective. The effects of PACAP38 on neuroblastoma cells may be a model for neurotrophic activities of PACAP38 via G protein‐linked intracellular messengers in human sympathoadrenal cells.

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