The neuromodulatory effects of VIP/PACAP on PC-12 cells are associated with their N-terminal structures.
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.
Onoue
S
S
Itoham Foods Inc., Central Research Institute, Moriya, 302-0104, Ibaraki, Japan. onoue@fureai.or.jp
Waki
Y
Y
Nagano
Y
Y
Satoh
S
S
Kashimoto
K
K
D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology; D009479:Neuropeptides / Q000494:pharmacology*; D016716:PC12 Cells; D010452:Peptide Biosynthesis; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D017434:Protein Structure, Tertiary; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014660:Vasoactive Intestinal Peptide / Q000737:chemistry
C495403:Adcyap1 protein, rat; D005456:Fluorescent Dyes; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide; D004121:Dimethyl Sulfoxide