Vasoactive intestinal peptide (VIP) has been considered as an autocrine
growth factor in
neuroblastomas. Pituitary
adenylate cyclase activating
polypeptides (PACAPs) are newly recognized members of the VIP family of
neurohormones. As compared to VIP,
PACAP has been reported to be biologically more potent and more efficient in tissues expressing selective
PACAP receptors rather than common VIP/
PACAP receptors. PACAPs and VIP interact with the same affinity and stimulate
adenylate cyclase activity with the same efficacy and potency on the
VIP receptors, but PACAPs act also on a more selective
PACAP receptor that also recognizes VIP but with a 100- to 1,000-fold lower affinity. Thus, depending on the type of receptors expressed at a cell surface,
PACAP may be more potent and efficient than VIP. The capacity of 22 surgical specimens of
neuroblastomas and of 5 established cell lines to synthesize
PACAP and VIP and to synthesize and express
PACAP receptors and
VIP receptors was studied. Using the
reverse transcriptase-polymerase chain (RT-PCR) method with specific primers, we detected the mRNAs coding for
PACAP and VIP in 19 and 3 out of 22 samples, respectively.
PACAP mRNA was expressed in 3 of the 5 cell lines studied and VIP
mRNA in 4. Using the same techniques,
PACAP and
VIP receptors mRNA were detected in 21, and 13 of the 22
tumor samples and in 5 and 1 of the cell lines studied, respectively. The expression of the
PACAP receptor was demonstrated by direct binding studies and/or by the relative potency of PACAPs and VIP to stimulate
adenylate cyclase activity in 16 of the 22
tumors and in all the cell lines. In addition, there was no correlation between
tumor stage and the expression of
mRNA coding for the
peptides and the receptors. The present results demonstrated that
PACAP could also be a candidate as an autocrine regulator of
neuroblastoma which a higher activity than VIP.