Impaired Pancreatic Ductal Bicarbonate Secretion in Cystic Fibrosis

Patients with cystic fibrosis demonstrate a defect in HCO3 - 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 HCO3 - transport in these cells. Recent functional and molecular studies indicate a major role for a basolateral electrogenically-driven Na+ :HCO3 - cotransporter (NBC1) in mediating the transport of HCO3 - into the duct cells. The HCO3 - exits at the lumen predominantly via two recently discovered apical HCO3 - transporters. cAMP, which mediates the stimulatory effect of secretin on pancreatic ductal HCO3 - secretion, potentiates the basolateral Na+ :HCO3 - 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 HCO3 - 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 HCO3 - 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 HCO3 - 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.


Manoocher Soleimani

Abstract | Full-Text | PDF

Share this  Facebook  Twitter  LinkedIn  Google+
30+ Million Readerbase
Flyer image
Abstracted/Indexed in
  • Index Copernicus
  • Academic Journals Database
  • Genamics JournalSeek
  • Academic Keys
  • China National Knowledge Infrastructure (CNKI)
  • CiteFactor
  • Scimago
  • British Library
  • Electronic Journals Library
  • Directory of Research Journal Indexing (DRJI)
  • WorldCat
  • Emerging Sources Citation Index (ESCI)
  • EBSCO Host
  • MIAR
  • International Committee of Medical Journal Editors (ICMJE)
  • University of Zurich - UZH
  • University Grants Commission
  • SWB Online-Katalog
  • Scholarsteer
  • Geneva Foundation for Medical Education and Research
  • Secret Search Engine Labs