Guanylin stimulates regulated secretion from human neuroendocrine pancreatic cells

Abstract

Background and 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 γ-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 coil heat-stable enterotoxin increased the release of chromogranin A and γ- 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.