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Titolo:
Guanylin in the human pancreas: a novel luminocrine regulatory pathway of electrolyte secretion via cGMP and CFTR in the ductal system
Autore:
Kulaksiz, H; Schmid, A; Honscheid, M; Eissele, R; Klempnauer, J; Cetin, Y;
Indirizzi:
Univ Marburg, Inst Anat & Cell Biol, Dept Mol Cell Biol, D-35033 Marburg, Germany Univ Marburg Marburg Germany D-35033 Cell Biol, D-35033 Marburg, Germany Univ Marburg, Dept Gastroenterol & Endocrinol, Marburg, Germany Univ Marburg Marburg Germany stroenterol & Endocrinol, Marburg, Germany Univ Saarland, Dept Physiol 2, D-6650 Homburg, Germany Univ Saarland Homburg Germany D-6650 Physiol 2, D-6650 Homburg, Germany Hannover Med Sch, Clin Visceral Surg, D-3000 Hannover, Germany Hannover Med Sch Hannover Germany D-3000 Surg, D-3000 Hannover, Germany Hannover Med Sch, Clin Transplantat Surg, D-3000 Hannover, Germany Hannover Med Sch Hannover Germany D-3000 Surg, D-3000 Hannover, Germany
Titolo Testata:
HISTOCHEMISTRY AND CELL BIOLOGY
fascicolo: 2, volume: 115, anno: 2001,
pagine: 131 - 145
SICI:
0948-6143(200102)115:2<131:GITHPA>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSMEMBRANE CONDUCTANCE REGULATOR; DEPENDENT PROTEIN-KINASE; HEAT-STABLE ENTEROTOXIN; CARBONIC-ANHYDRASE-II; CELL-LINE CAPAN-1; CYSTIC-FIBROSIS; FUNCTIONAL EXPRESSION; CL-/HCO3 EXCHANGE; HCO3 SECRETION; CYCLASE;
Keywords:
pancreas; regulatory peptides; guanylate cyclase; protein kinase; anion exchanger;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Cetin, Y Univ Marburg, Inst Anat & Cell Biol, Dept Mol Cell Biol, Robert Koch Str 6, D-35033 Marburg, Germany Univ Marburg Robert Koch Str 6 MarburgGermany D-35033 , Germany
Citazione:
H. Kulaksiz et al., "Guanylin in the human pancreas: a novel luminocrine regulatory pathway of electrolyte secretion via cGMP and CFTR in the ductal system", HISTOCHEM C, 115(2), 2001, pp. 131-145

Abstract

Cystic fibrosis transmembrane conductance regulator (CFTR) is a channel and regulator protein that is crucially involved in transepithelial ion transport. In the exocrine pancreas, the CFTR-mediated secretion of an electrolyte-rich fluid is a major but as yet incompletely understood function. We show here that the peptide guanylin is a specific activator of CFTR function in the human pancreas implicating regulation of pancreatic electrolyte secretion. Guanylin and its affiliated signaling and effector proteins including guanylate cyclase C, cGMP-dependent protein kinase II, CFTR, and the epithelial Cl-/HCO3- exchanger, anion exchanger 2, are highly expressed in the human pancreas. Guanylin is localized specifically to the typical centroacinar cells and proximal duct cells which, based on its additional presence in the pancreatic juice, is obviously released luminally into the pancreaticducts. The guanylin receptor and the respective functional downstream proteins are all confined to the apical membrane of the duct cells implicating an as yet unknown route of luminal regulatory pathway of electrolyte secretion in the ductal system. Functional studies in two different human pancreatic duct cell lines expressing the CFTR Cl- channel that is functionally intact in CAPAN-1 cells but defective (Delta F508) in CFPAC-1 cells clearly identify guanylin as a specific regulator of pancreatic CFTR channel function. Whole-cell patch-clamp recordings in CAPAN-1 cells revealed that forskolin induces an increase of Cl- conductance mediated by cAMP. In contrast, guanylin in creased Cl- conductance in the same cells via cGMP but not cAMP; the respective membrane current was largely blockable by the sulfonylurea glibenclamide. In CFPAC-1 cells, however, neither guanylin nor forskolin produced a current activation. Based on the present findings we conclude that guanylin is an intrinsic pancreatic regulator of Cl- current activation in pancreatic duct cells via cGMP and CFTR. Remarkably, in the pancreas guanylin may exert its function through an intriguing luminocrine mode via the pancreatic juice.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/03/20 alle ore 23:18:56