Abstract:
BACKGROUND & AIMS: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.
journal_name
Gastroenterologyjournal_title
Gastroenterologyauthors
John M,Wiedenmann B,Kruhøffer M,Adermann K,Ankorina-Stark I,Schlatter E,Ahnert-Hilger G,Forssmann WG,Kuhn Mdoi
10.1016/s0016-5085(98)70593-1subject
Has Abstractpub_date
1998-04-01 00:00:00pages
791-7issue
4eissn
0016-5085issn
1528-0012pii
S0016508598003382journal_volume
114pub_type
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