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.
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 humanpancreatic 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: Khaldoun Almhanna; David Wright; Teresa Macarulla Mercade; Jean-Luc Van Laethem; Antonio Cubillo Gracian; Carmen Guillen-Ponce; Jason Faris; Carolina Muriel Lopez; Richard A Hubner; Johanna Bendell; Alain Bols; Jaime Feliu; Naureen Starling; Peter Enzinger; Devalingham Mahalingham; Wells Messersmith; Huyuan Yang; Adedigbo Fasanmade; Hadi Danaee; Thea Kalebic Journal: Invest New Drugs Date: 2017-05-19 Impact factor: 3.850
Authors: Anna R Schreiber; Anna Nguyen; Stacey M Bagby; John J Arcaroli; Betelehem W Yacob; Kevin Quackenbush; Joe L Guy; Thomas Crowell; Bradley Stringer; Hadi Danaee; Thea Kalebic; Wells A Messersmith; Todd M Pitts Journal: Clin Cancer Drugs Date: 2018
Authors: Adam E Snook; Trevor R Baybutt; Bo Xiang; Tara S Abraham; John C Flickinger; Terry Hyslop; Tingting Zhan; Walter K Kraft; Takami Sato; Scott A Waldman Journal: J Immunother Cancer Date: 2019-04-23 Impact factor: 13.751
Authors: Melissa Gallery; Julie Zhang; Daniel P Bradley; Pamela Brauer; Donna Cvet; Jose Estevam; Hadi Danaee; Edward Greenfield; Ping Li; Mark Manfredi; Huay-Keng Loke; Claudia Rabino; Brad Stringer; Mark Williamson; Tim Wyant; Johnny Yang; Qing Zhu; Adnan Abu-Yousif; O Petter Veiby Journal: PLoS One Date: 2018-01-25 Impact factor: 3.240