GUANYLIN STIMULATES REGULATED SECRETION FROM HUMAN NEUROENDOCRINE PANCREATIC-CELLS

Background & Aims: Gastroenteropancreatic neuroendocrine cells secrete chemical messengers in a calcium-dependent fashion. So far, other sec ond messenger systems involved in regulated secretion have gained litt le attention. The aim of this study was to characterize guanosine 3',5 '-cyclic monophosphate (cGMP)-mediated vesicular secretion in pancreat ic neuroendocrine cells. Methods: In a human pancreatic cell line, BON , cyclic nucleotide levels and chromogranin A release were monitored w ith specific immunoassays. Uptake and release of gamma-aminobutyric ac id were measured, Intracellular Ca2+ concentration was monitored with fura-2. Guanylyl cyclase C was analyzed by reverse-transcription polym erase chain reaction. Results: Guanylin increased cGMP concentrations in BON cells via guanylyl cyclase C. Stimulation of the cGMP pathway b y guanylin or Escherichia coli heat-stable enterotoxin increased the r elease of chromogranin A and gamma-aminobutyric acid from BON cells. T his effect was mimicked by the cGMP analogue 8-bromo-cGMP. Conclusions : Guanylin and STa stimulate the regulated secretion from BON cells vi a guanylyl cyclase C and cGMP. Our study yields novel information abou t secretory properties of guanylin, mediated via a signal transduction pathway, increasing cGMP and leading to regulated secretion of neuroe ndocrine cells.