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Cyclic AMP Formation in C6 Glioma Cells
Author(s) -
SOKOLOWSKA PAULINA,
NOWAK JERZY Z.
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1317.082
Subject(s) - vasoactive intestinal peptide , forskolin , ibmx , receptor , pituitary adenylate cyclase activating peptide , adenylyl cyclase , agonist , endocrinology , medicine , adenylate kinase , isoprenaline , cyclase , biology , chemistry , neuropeptide , stimulation
Abstract: Pituitary adenylate cyclase‐activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) exert their actions via common receptors, VPAC1 and VPAC2, which are equally sensitive to both peptides, while PACAP stimulates its specific PAC1‐type receptors. Both peptides potently stimulate cAMP production in different biological systems. In the present article, we examined the effects of PACAP and VIP on cAMP formation in C6 rat glioma cells used between passages 12‐28 (early) and 120‐136 (late). In the presence of the PDE inhibitor IBMX (0.1 mM), PACAP (0.1 μM) and VIP (1 μM) strongly stimulated cAMP synthesis in C6 cells in early passages, but not in C6 cells in late passages. In contrast, forskolin (10 μM), a direct activator of adenylyl cyclase, and isoprenaline (10 μM), a β‐adrenergic receptor agonist, strongly stimulated cAMP production in both early and late C6 cell passages. Concentration‐dependent studies carried out in early passages with PACAP‐38, PACAP‐27, mammalian and chicken VIPs, and PHI/PHM peptides (1–5 μM) revealed that both forms of PACAP produced strong cAMP accumulation, VIP peptides were less effective than PACAP, while the cAMP effects of PHI/PHM peptides were noticeable only at the highest doses tested. These results suggest that C6 glioma cells in early passages possess functional PAC1 and possibly VPAC‐type receptors, but either the density of PACAP/VIP receptors progressively declines or the PACAP/VIP receptor‐Gs protein coupling becomes less effective through culture passages.