Effects of PACAP and VIP on cAMP-generating System and Proliferation of C6 Glioma Cells

• Published in: Journal of molecular neuroscience Vol. 36; no. 1-3; pp. 286 - 291
• Main Authors: Sokolowska, Paulina, Nowak, Jerzy Z.
• Format: Journal Article
• Language: English
• Published: New York Humana Press Inc 01.11.2008; Springer Nature B.V
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Bucladesine - metabolism; Cell Biology; Cell Line, Tumor - drug effects; Cell Proliferation - drug effects; Colforsin - pharmacology; Cyclic AMP - metabolism; Enzyme Inhibitors - pharmacology; Neurochemistry; Neurology; Neurosciences; Peptide Fragments - pharmacology; Peptides; Peptides - pharmacology; Pituitary Adenylate Cyclase-Activating Polypeptide - pharmacology; Proteomics; Rats; Secretin - metabolism; Vasoactive Intestinal Peptide - pharmacology; Proliferation; PACAP; VIP; cAMP; Rat glioma cells
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-008-9071-9

An identification of PAC 1 - and VPAC-type receptors in a great number of neoplastic cells gave rise to intensive studies on the biochemical and physiological role of the mentioned peptides in cancers. Our earlier studies focused on effects of pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) in C6 glioma cells have shown their stimulatory receptor-mediated action on the cyclic adenosine monophosphate (cAMP)-generating system. In the present study, we demonstrated that truncated peptides, i.e., PACAP6-38 and VIP6-28, both produced a significant inhibition of the VIP-induced increase in cAMP production, whereas only PACAP6-38 did antagonize the PACAP-38 effect. In contrast to the well-expressed PACAP-38 and VIP effects on cAMP production in C6 cells, helodermin and secretin were poorly active as cAMP stimulators in this cell line, displaying some activity only at a high 5-μM dose. PACAP-38 and, to a lesser extent VIP stimulated the proliferation of C6 glioma cells, which was shown by an increased incorporation of 3 H-thymidine into the cells, and the effects of these two peptides were antagonized by PACAP6-38. The truncated PACAP (10 μM) by itself significantly inhibited C6 cell proliferation. The study with the use of forskolin and dibutyryl-cAMP revealed that the growth effects of PACAP were cAMP independent. Our findings suggest that glioma C6 cells possess PAC 1 - and VPAC-type receptors, but the density of PAC 1 seems to be much larger than VPAC receptors. Although the proliferative activity of PACAP and VIP is mediated via the PAC 1 -type receptor, the signaling cascade underlying this phenomenon does not seem to involve cAMP.