Pancreatic ductal bicarbonate secretion: past, present and future.
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.
Ishiguro
H
H
Departments of Internal Medicine II and Human Nutrition, Nagoya University School of Medicine, Nagoya, Japan.
Naruse
S
S
San Román
J I
JI
Case
M
M
Steward
M C
MC
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D003592:Cytophotometry; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D008954:Models, Biological; D010183:Pancreatic Ducts / Q000378:metabolism*; D010477:Perfusion; D028021:Sodium-Potassium-Chloride Symporters / Q000502:physiology
D001639:Bicarbonates; D002712:Chlorides; D028021:Sodium-Potassium-Chloride Symporters