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

• Published in: Peptides (New York, N.Y. : 1980) Vol. 22; no. 6; pp. 867 - 872
• Main Authors: Onoue, Satomi, Waki, Yoshihiro, Nagano, Yumiko, Satoh, Seiji, Kashimoto, Kazuhisa
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2001
• Subjects: Amino Acid Sequence; Animals; Cell Division; Dimethyl Sulfoxide - pharmacology; Dose-Response Relationship, Drug; Fluorescent Dyes - pharmacology; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular dynamics; Molecular Sequence Data; Neurite outgrowth; Neurons - cytology; Neuropeptides; Neuropeptides - pharmacology; PACAP; PC-12 cells; PC12 Cells; Peptide Biosynthesis; Pituitary Adenylate Cyclase-Activating Polypeptide; Protein Structure, Tertiary; Rats; Sequence Homology, Amino Acid; Structure-activity relationships; Vasoactive Intestinal Peptide - chemistry; VIP; PACAP; Molecular dynamics; Neuropeptides; PC-12 cells; VIP; Structure-activity relationships; Neurite outgrowth
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/S0196-9781(01)00411-9

ONOUE, S., WAKI, Y., NAGANO, Y., SATOH, S., KASHIMOTO, K. Neuromodulatory Effects of VIP/PACAP on PC-12 Cells Are Associated with Their N-terminal Structures. PEPTIDES xx(xx) 000–000, 200x.– The current study explored whether the differences in biological activities in PC-12 cells between vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are attributable to the sequence difference in their N-terminal portions and are correlated with the solution structures of the peptides. In the neurite outgrowth assay, N-terminal modification of VIP to PACAP-like sequences altered its effect, the activity was confirmed even at a low concentration (10 −10 M). On the contrary, N-terminal modification of PACAP 27 to VIP-like sequences reduced its activity. These relationships were also confirmed for the inhibitory effects of the peptide analogues on PC-12 cells growth at 10 −7 M. The present results combined with our previously reported data, including binding assay, support that the N-termini of VIP/PACAP plays an important role in their activities.