title: CO2 permeability and bicarbonate transport in microperfused interlobular ducts isolated from guinea-pig pancreas.
abstract: Permeabilities of the luminal and basolateral membranes of pancreatic duct cells to CO2 and HCO3- were examined in interlobular duct segments isolated from guinea-pig pancreas. Intracellular pH (pHi) was measured by microfluorometry in unstimulated, microperfused ducts loaded with the pH-sensitive fluoroprobe 2'7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF). When HCO3-/CO2 was admitted to the bath, pHi decreased transiently as a result of CO2 diffusion and then increased to a higher value as a result of HCO3- uptake across the basolateral membrane by Na+-HCO3- cotransport. When HCO3-/CO2 was admitted to the lumen, pHi again decreased but no subsequent increase was observed, indicating that the luminal membrane was permeable to CO2 but did not allow HCO3- entry to the cells from the lumen. Only when the luminal HCO3- concentration was raised above 125 mM was HCO3- entry detected. The same was true of duct cells stimulated with forskolin. Recovery of pHi from an acid load, induced by exposure to an NH4+ pulse, was dependent on basolateral but not luminal Na+ and could be blocked by basolateral application of methylisobutylamiloride and H2DIDS. This indicates that the Na+-H+ exchangers and Na+-HCO3- cotransporters are located exclusively at the basolateral membrane. In the presence of HCO3-/CO2, substitution of basolateral Cl- with glucuronate caused larger increases in pHi than substitution of luminal Cl-. This suggests that the anion exchanger activity in the basolateral membrane is greater than that in the luminal membrane. We conclude that the luminal and basolateral membranes are both freely permeable to CO2, but while the basolateral membrane has both uptake and efflux pathways for HCO3-, the luminal membrane presents a significant barrier to the re-entry of secreted HCO3-, largely through the inhibition of the luminal anion exchanger by high luminal HCO3- concentrations.
authors.affiliation: Internal Medicine II, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. hishigu@med.nagoya-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Ishiguro
authors.forename: S
authors.initials: S
authors.lastname: Naruse
authors.forename: M
authors.initials: M
authors.lastname: Kitagawa
authors.forename: A
authors.initials: A
authors.lastname: Suzuki
authors.forename: A
authors.initials: A
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Hayakawa
authors.forename: R M
authors.initials: RM
authors.lastname: Case
authors.forename: M C
authors.initials: MC
authors.lastname: Steward
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism* / Q000494:pharmacology; D001693:Biological Transport, Active; D002245:Carbon Dioxide / Q000378:metabolism* / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D007474:Ion Exchange; D008566:Membranes / Q000378:metabolism; D010183:Pancreatic Ducts / Q000187:drug effects / Q000378:metabolism*; D010477:Perfusion; D010539:Permeability; D012964:Sodium / Q000378:metabolism
chemical_list: D001639:Bicarbonates; D002712:Chlorides; D002245:Carbon Dioxide; D012964:Sodium