title: Guanylin stimulates regulated secretion from human neuroendocrine pancreatic cells.
abstract: OBJECTIVE
  Gastroenteropancreatic neuroendocrine cells secrete chemical messengers in a calcium-dependent fashion. So far, other second messenger systems involved in regulated secretion have gained little attention. The aim of this study was to characterize guanosine 3',5'-cyclic monophosphate (cGMP)-mediated vesicular secretion in pancreatic neuroendocrine cells.
  
  
  METHODS
  In a human pancreatic cell line, BON, cyclic nucleotide levels and chromogranin A release were monitored with specific immunoassays. Uptake and release of gamma-aminobutyric acid were measured. Intracellular Ca2+ concentration was monitored with fura-2. Guanylyl cyclase C was analyzed by reverse-transcription polymerase chain reaction.
  
  
  RESULTS
  Guanylin increased cGMP concentrations in BON cells via guanylyl cyclase C. Stimulation of the cGMP pathway by guanylin or Escherichia coli heat-stable enterotoxin increased the release of chromogranin A and gamma-aminobutyric acid from BON cells. This effect was mimicked by the cGMP analogue 8-bromo-cGMP.
  
  
  CONCLUSIONS
  Guanylin and STa stimulate the regulated secretion from BON cells via guanylyl cyclase C and cGMP. Our study yields novel information about secretory properties of guanylin, mediated via a signal transduction pathway, increasing cGMP and leading to regulated secretion of neuroendocrine cells.
authors.affiliation: Department of Gastroenterology, Klinikum Benjamin Franklin, Freie Universität Berlin, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: John
authors.forename: B
authors.initials: B
authors.lastname: Wiedenmann
authors.forename: M
authors.initials: M
authors.lastname: Kruhøffer
authors.forename: K
authors.initials: K
authors.lastname: Adermann
authors.forename: I
authors.initials: I
authors.lastname: Ankorina-Stark
authors.forename: E
authors.initials: E
authors.lastname: Schlatter
authors.forename: G
authors.initials: G
authors.lastname: Ahnert-Hilger
authors.forename: W G
authors.initials: WG
authors.lastname: Forssmann
authors.forename: M
authors.initials: M
authors.lastname: Kuhn
mesh_terms: D001427:Bacterial Toxins / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism; D006152:Cyclic GMP / Q000032:analysis; D004768:Enterotoxins / Q000494:pharmacology; D029968:Escherichia coli Proteins; D005768:Gastrointestinal Hormones; D006801:Humans; D045265:Natriuretic Peptides; D009490:Neurosecretory Systems / Q000187:drug effects*; D010190:Pancreatic Neoplasms / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D053379:Chromogranin A; D002864:Chromogranins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D005768:Gastrointestinal Hormones; D045265:Natriuretic Peptides; D010455:Peptides; D012333:RNA, Messenger; C034151:heat stable toxin (E coli); C072685:guanylin; D005680:gamma-Aminobutyric Acid; D006152:Cyclic GMP; D002118:Calcium