(Journal Article): Pancreatic Ductal Bicarbonate Secretion: Past, Present and Future
 
Ishiguro H, Naruse S, San Román JI, Case M, Steward MC (Depts of Internal Medicine II and Human Nutrition, Nagoya University School of Medicine. Nagoya, Japan, School of Biological Sciences, University of Manchester. UK. Departamento de Fisiologia y Farmacologia, Universidad de Salamanca. Salamanca, Spain, martin.steward@man.ac.uk )
 
IN: JOP. J Pancreas (Online) 2001; 02(4 Suppl.):192-197

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ABSTRACT: The pancreatic duct epithelium in the guinea-pig and many other species secretes HCO(3)(-) at concentrations approaching 150 mM. This cannot be explained by conventional models based upon HCO(3)(-) secretion via an anion exchanger at the luminal membrane because: 1) under these conditions, the Cl(-) and HCO(3)(-) concentration gradients would favour HCO(3)(-) reabsorption rather than secretion, and 2) the luminal anion exchanger appears to be inhibited by luminal HCO(3)(-) concentrations of 125 mM or more. There may, however, be a sufficiently large electrochemical gradient to drive HCO(3)(-) secretion across the luminal membrane via an anion conductance. In contrast to earlier studies on rat ducts, the membrane potential E(m) in guinea-pig duct cells does not depolarise appreciably upon stimulation with secretagogues but remains constant at about -60 mV. Consequently, even with 125 mM or more HCO(3)(-) in the lumen and an estimated 20 mM in the cytoplasm, the electrochemical gradient for HCO(3)(-) will still favour secretion to the lumen. Under the same conditions, the intracellular Cl(-) concentration drops to very low levels (approximately 7 mM) presumably because, although Cl(-) may leave freely through the cystic fibrosis transmembrane conductance regulator (CFTR) channels in the luminal membrane, there is no major pathway for Cl(-) uptake across the basolateral membrane. Consequently a HCO(3)(-)-rich secretion may arise as a result of the lack of competition from intracellular Cl(-) for efflux via the anion conductances at the luminal membrane. Whether CFTR, or another anion conductance, provides such a pathway for HCO(3)(-) remains to be seen.

TYPE OF PUBLICATION: Round Table