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Impaired Pancreatic Ductal Bicarbonate Secretion in Cystic Fibrosis
 
Diabetes OD > Journals > JOP > 2001 > Journal Article

(Journal Article): Impaired Pancreatic Ductal Bicarbonate Secretion in Cystic Fibrosis
 
Soleimani M (Department of Medicine, University of Cincinnati, and Veterans Affairs Medical Center at Cincinnati. Cincinnati, OH, USA, manoocher.soleimani@uc.edu )
 
IN: JOP. J Pancreas (Online) 2001; 02(4 Suppl.):237-242

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ABSTRACT: Patients with cystic fibrosis demonstrate a defect in HCO(3)(-) secretion by their pancreatic duct cells. However, attempts toward understanding or correcting this defect have been hampered by a lack of knowledge regarding the cellular and molecular mechanisms mediating HCO(3)(-) transport in these cells. Recent functional and molecular studies indicate a major role for a basolateral electrogenically-driven Na(+):HCO(3)(-) cotransporter (NBC1) in mediating the transport of HCO(3)(-) into the duct cells. The HCO(3)(-) exits at the lumen predominantly via two recently discovered apical HCO(3)(-) transporters. cAMP, which mediates the stimulatory effect of secretin on pancreatic ductal HCO(3)(-) secretion, potentiates the basolateral Na(+):HCO(3)(-) cotransporter due to generation of a favorable electrogenic gradient as a result of membrane depolarization by Cl(-)-secreting cystic fibrosis transmembrane conductance regulator (CFTR). Two apical HCO(3)(-) transporters drive the secretion of bicarbonate into the pancreatic duct lumen. Molecular and functional studies indicate that CFTR upregulates the expression of these two apical HCO(3)(-) transporters. In addition, CFTR may also upregulate the expression of certain water channels and facilitate the secretion of fluid into the duct lumen. In brief, current research suggests that the defect in pancreatic HCO(3)(-) secretion in patients with cystic fibrosis is multifactorial and involves the alteration in the function/expression of transporters at the basolateral and luminal membrane domains of the duct cells.

TYPE OF PUBLICATION: Round Table



 
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