title: A fundamental role for NO-PLC signaling pathway in mediating intracellular Ca2+ oscillation in pancreatic acini.
abstract: The aim of the present study was to investigate the possible interaction between intracellular Ca(2+) and nitric oxide (NO) in rat pancreatic acinar cells, especially intracellular signaling events. (1) Nitric oxide donors SNP (0.1-100 μM) and NOR-3 (50-400 μM) induced Ca(2+) oscillations in fluo-4-loaded acini, that appeared to be analogous to what we usually observe in acini stimulated with physiological secretagogues such as CCK-8 and this oscillations were abolished in the presence of carboxy-PTIO. (2) The NO donors-evoked Ca(2+) oscillations were not abolished even in the absence of extracellular Ca(2+) but totally disappeared when cells were pretreated with thapsigargin, a sarcoplasmic-endoplasmic reticulum Ca(2+) ATPase (SERCA) inhibitor. (3) Inhibition of guanylate cyclase with 1 H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) attenuated Ca(2+) oscillations evoked by SNP in the absence of extracellular Ca(2+). (4) Inhibitors of phospholipase C activity, U73122 and the IP(3)R blocker xestospongin C, both abolished the SNP-induced Ca(2+) response. (5) Furthermore, we found that both CCK-8 and carbachol (CCh) induced NO production in DAF-2-loaded acinar cells and that an inhibitor of NO synthase, N(G)-monomethyl-l-arginine (L-NMMA), significantly reduced CCK-8-induced Ca(2+) oscillation. These results indicate that NO mobilizes Ca(2+) from internal stores through activation of guanylate cyclase and resultant cGMP production. In addition, PLC activation of IP(3) production is also suggested to be involved in Ca(2+) mobilization via IP(3) receptors. This suggests the presence of cross-talk between Ca(2+) and NO in pancreatic acini and this cascade may, at least partially, participate in physiological secretagogue-evoked Ca(2+) dynamics in pancreatic acinar cells.
authors.affiliation: Laboratory of Physiology, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Amira
authors.initials: A
authors.lastname: Moustafa
authors.forename: Kentaro Q
authors.initials: KQ
authors.lastname: Sakamoto
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Habara
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D018267:Carcinoma, Acinar Cell / Q000378:metabolism*; D004963:Estrenes / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism; D047028:Macrocyclic Compounds / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D012844:Sincalide / Q000378:metabolism; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004963:Estrenes; D047028:Macrocyclic Compounds; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D010080:Oxazoles; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D011810:Quinoxalines; C511704:xestospongin C; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D009599:Nitroprusside; D009569:Nitric Oxide; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D012844:Sincalide; D002118:Calcium