Effects of PACAP and VIP on cAMP-generating system and proliferation of C6 glioma cells.
An identification of PAC1- 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-microM dose. PACAP-38 and, to a lesser extent VIP stimulated the proliferation of C6 glioma cells, which was shown by an increased incorporation of 3H-thymidine into the cells, and the effects of these two peptides were antagonized by PACAP6-38. The truncated PACAP (10 microM) 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 PAC1- and VPAC-type receptors, but the density of PAC1 seems to be much larger than VPAC receptors. Although the proliferative activity of PACAP and VIP is mediated via the PAC1-type receptor, the signaling cascade underlying this phenomenon does not seem to involve cAMP.
Sokolowska
Paulina
P
Centre for Medical Biology, Polish Academy of Sciences, Lodz, 93-232, Poland. psokolowska@cbm.pan.pl
Nowak
Jerzy Z
JZ
D000818:Animals; D003994:Bucladesine / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D051381:Rats; D012633:Secretin / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D010455:Peptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; C075647:pituitary adenylate-cyclase-activating-peptide (6-38); C113198:vasoactive intestinal peptide (6-28); D012633:Secretin; D005576:Colforsin; D014660:Vasoactive Intestinal Peptide; D003994:Bucladesine; C040442:heliodermin; D000242:Cyclic AMP