title: Pituitary adenylate cyclase-activating peptide stimulates cyclic AMP accumulation in UMR 106 osteoblast-like cells.
abstract: Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) share 68% homology and function as neurotransmitters or neuroendocrine factors. Although VIP immunoreactivity has been detected in bone cells, the presence of PACAP or PACAP receptors in bone has not been determined. In this study, we investigated the role of PACAP and VIP in regulating cAMP accumulation in the UMR 106 osteoblast-like tumor cell line. PACAP 27 (10(-9) to 3 x 10(-7) M), PACAP 38 (10(-9) to 3 x 10(-7) M) and VIP (10(-8) to 10(-6) M) stimulated cAMP accumulation up to eightfold. PACAP 27 was slightly more potent than PACAP 38, and both were tenfold more potent than VIP. Both PACAP- and VIP-stimulated cAMP accumulation were potentiated by 4 beta-phorbol 12-myristate 13-acetate, an activator of protein kinase C. Two PACAP antagonists, PACAP 6-27 (3 x 10(-6) M) and PACAP 6-38 (3 x 10(-6) M), blocked PACAP- and VIP-stimulated cAMP accumulation. Two VIP antagonists ([Lys1,Pro2,5,Arg3,4,Tyr6]-VIP, and [4 Cl-D-Phe6,Leu17]-VIP) did not reduce the PACAP- or VIP-stimulated cAMP accumulation. Pretreatment with PACAP 27, PACAP 38 or VIP equally blocked PACAP- and VIP-stimulated cAMP accumulation. These results suggest that PACAP is a more potent stimulator of cAMP accumulation than VIP in UMR 106 cells. PACAP and VIP may share a role in the paracrine or neuroendocrine regulation of bone metabolism.
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Canada.
authors.forename: C S
authors.initials: CS
authors.lastname: Kovacs
authors.forename: C L
authors.initials: CL
authors.lastname: Chik
authors.forename: B
authors.initials: B
authors.lastname: Li
authors.forename: E
authors.initials: E
authors.lastname: Karpinski
authors.forename: A K
authors.initials: AK
authors.lastname: Ho
mesh_terms: D000242:Cyclic AMP / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011493:Protein Kinase C / Q000378:metabolism; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: C495401:ADCYAP1 protein, human; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; C075647:pituitary adenylate-cyclase-activating-peptide (6-38); C100831:vasoactive intestinal peptide, Lys(1)-Pro(2,5)-Arg(3,4)-Tyr(6)-; C048507:vasoactive intestinal peptide, 4-chloro-Phe(6)-Leu(17)-; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate