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A fundamental role for NO-PLC signaling pathway in mediating intracellular Ca2+ oscillation in pancreatic acini
Faculty
Veterinary Medicine
Year:
2011
Type of Publication:
Article
Pages:
139-150
Authors:
Moustafa, Amira, Sakamoto, Kentaro Q, Habara, Yoshiaki
DOI:
10.1016/j.niox.2011.02.001
Journal:
NITRIC OXIDE-BIOLOGY AND CHEMISTRY ACADEMIC PRESS INC ELSEVIER SCIENCE
Volume:
24
Research Area:
Biochemistry \& Molecular Biology; Cell Biology
ISSN
ISI:000289825600004
Keywords :
Nitric oxide, Ca2+ oscillation, Acinar cell, Pancreas, cGMP, DAF-2/DA
Abstract:
The aim of the present study was to investigate the possible interaction between intracellular Ca2+ and nitric oxide (NO) in rat pancreatic acinar cells, especially intracellular signaling events. (1) Nitric oxide donors SNP (0.1-100 mu M) and NOR-3 (50-400 mu M) induced Ca2+ 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 Ca2+ oscillations were not abolished even in the absence of extracellular Ca2+ but totally disappeared when cells were pretreated with thapsigargin, a sarcoplasmic-endoplasmic reticulum Ca2+ ATPase (SERCA) inhibitor. (3) Inhibition of guanylate cyclase with 1 H-{[}1,2,4] oxadiazolo {[}4,3-a] quinoxaline-1-one (ODQ) attenuated Ca2+ oscillations evoked by SNP in the absence of extracellular Ca2+ (4) Inhibitors of phospholipase C activity, U73122 and the IP3R blocker xestospongin C, both abolished the SNP-induced Ca2+ 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 Ca2+ oscillation. These results indicate that NO mobilizes Ca2+ from internal stores through activation of guanylate cyclase and resultant cGMP production. In addition, PLC activation of IP3 production is also suggested to be involved in Ca2+ mobilization via IP3 receptors. This suggests the presence of cross-talk between Ca2+ and NO in pancreatic acini and this cascade may, at least partially, participate in physiological secretagogue-evoked Ca2+ dynamics in pancreatic acinar cells. (C) 2011 Elsevier Inc. All rights reserved.
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