title: Serotonin regulates amylase secretion and acinar cell damage during murine pancreatitis.
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.
authors.affiliation: Department of Visceral and Transplantation Surgery, Swiss Hepato-Pancreato-Biliary Center, University Hospital, Zurich 8091, Switzerland. sabrina.sonda@usz.ch
authors.forename: Sabrina
authors.initials: S
authors.lastname: Sonda
authors.forename: Alberto B
authors.initials: AB
authors.lastname: Silva
authors.forename: Kamile
authors.initials: K
authors.lastname: Grabliauskaite
authors.forename: Enrica
authors.initials: E
authors.lastname: Saponara
authors.forename: Achim
authors.initials: A
authors.lastname: Weber
authors.forename: Jae-Hwi
authors.initials: JH
authors.lastname: Jang
authors.forename: Richard A
authors.initials: RA
authors.lastname: Züllig
authors.forename: Martha
authors.initials: M
authors.lastname: Bain
authors.forename: Theresia
authors.initials: T
authors.lastname: Reding Graf
authors.forename: Adrian B
authors.initials: AB
authors.lastname: Hehl
authors.forename: Rolf
authors.initials: R
authors.lastname: Graf
mesh_terms: D061354:Acinar Cells / Q000201:enzymology / Q000473:pathology*; D008841:Actin Cytoskeleton / Q000473:pathology; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002108:Ceruletide / Q000009:adverse effects; D002634:Chemotaxis, Leukocyte; D018450:Disease Progression; D004792:Enzyme Precursors / Q000378:metabolism*; D005355:Fibrosis; D007150:Immunohistochemistry; D007249:Inflammation / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010195:Pancreatitis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D012701:Serotonin / Q000502:physiology*
chemical_list: D004792:Enzyme Precursors; D012701:Serotonin; D002108:Ceruletide; D000681:Amylases