The neuromodulatory effects of VIP/PACAP on PC-12 cells are associated with their N-terminal structures

The current study explored whether the differences in biological activities in PC-12 cells between vasoactive intestinal polypeptide (VIP) and pituita ry adenylate cyclase-activating polypeptide (PACAP) are attributable to the sequence difference in their N-terminal portions and are correlated with t he solution structures of the peptides. In the neurite outgrowth assay, N-t erminal modification of VIP to PACAP-like sequences altered its effect, the activity was confirmed even at a low concentration (10(-10) M). On the con trary, N-terminal modification of PACAP 27 to VIP-like sequences reduced it s activity. These relationships were also confirmed for the inhibitory effe cts: of the peptide analogues on PC-12 cells growth at 10(-7) M. The presen t results combined with our previously reported data, including binding ass ay, support that the N-termini of VIP/PACAP plays an important role in thei r activities. (C) 2001 Elsevier Science Inc. All rights reserved.