Serotonin regulates amylase secretion and acinar cell damage during murine pancreatitis

Sonda, Sabrina, Silva, Alberto B., Grabliauskaite, Kamile, Saponara, Enrica, Weber, Achim, Jang, Jae-Hwi, Züllig, Richard A., Bain, Martha, Graf, Theresia Reding, Hehl, Adrian B. and Graf, Rolf (2012) Serotonin regulates amylase secretion and acinar cell damage during murine pancreatitis. Gut, 62 6: 890-898. doi:10.1136/gutjnl-2011-301724

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Author Sonda, Sabrina
Silva, Alberto B.
Grabliauskaite, Kamile
Saponara, Enrica
Weber, Achim
Jang, Jae-Hwi
Züllig, Richard A.
Bain, Martha
Graf, Theresia Reding
Hehl, Adrian B.
Graf, Rolf
Title Serotonin regulates amylase secretion and acinar cell damage during murine pancreatitis
Journal name Gut   Check publisher's open access policy
ISSN 0017-5749
Publication date 2012
Sub-type Article (original research)
DOI 10.1136/gutjnl-2011-301724
Volume 62
Issue 6
Start page 890
End page 898
Total pages 11
Place of publication London, U.K.
Publisher BMJ Group
Collection year 2013
Language eng
Formatted abstract
Objective Serotonin (5-hydroxytryptamine, 5-HT) is a potent bioactive molecule involved in a variety of physiological processes. In this study, the authors analysed whether 5-HT regulates zymogen secretion in pancreatic acinar cells and the development of pancreatic inflammation, a potentially lethal disease whose pathophysiology is not completely understood.

Methods 5-HT regulation of zymogen secretion was analysed in pancreatic acini isolated from wild-type or tryptophan hydoxylase-1 knock-out (TPH1−/−) mice, which lack peripheral 5-HT, and in amylase-secreting pancreatic cell lines. Pancreatitis was induced by cerulein stimulation and biochemical and immunohistochemical methods were used to evaluate disease progression over 2 weeks.

Results Absence and reduced intracellular levels of 5-HT inhibited the secretion of zymogen granules both ex vivo and in vitro and altered cytoskeleton dynamics. In addition, absence of 5-HT resulted in attenuated pro-inflammatory response after induction of pancreatitis. TPH1−/− mice showed limited zymogen release, reduced expression of the pro-inflammatory chemokine MCP-1 and minimal leucocyte infiltration compared with wild-type animals. Restoration of 5-HT levels in TPH1−/− mice recovered the blunted inflammatory processes observed during acute pancreatitis. However, cellular damage, inflammatory and fibrotic processes accelerated in TPH1−/− mice during disease progression.

Conclusions These results identify a 5-HT-mediated regulation of zymogen secretion in pancreatic acinar cells. In addition, they demonstrate that 5-HT is required for the onset but not for the progression of pancreatic inflammation. These findings provide novel insights into the normal physiology of pancreatic acinar cells and into the pathophysiology of pancreatitis, with potential therapeutic implications.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ
Additional Notes Published Online First 16 May 2012

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 7 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 29 May 2012, 14:03:53 EST by Alberto Boucas Da Silva on behalf of Institute for Molecular Bioscience