Basolateral anion transport mechanisms underlying fluid secretion by mouse, rat and guinea-pig pancreatic ducts

• Published in: The Journal of physiology Vol. 556; no. 2; pp. 415 - 428
• Main Authors: Fernández‐Salazar, M. Paz, Pascua, Patricia, Calvo, José Julián, López, María A., Case, R. Maynard, Steward, Martin C., San Román, José I.
• Format: Journal Article
• Language: English
• Published: 9600 Garsington Road , Oxford , OX4 2DQ , UK The Physiological Society 15.04.2004; Blackwell Science Ltd; Blackwell Science Inc
• Subjects: Animals; Anions - pharmacokinetics; Bicarbonates - pharmacokinetics; Biological Transport - drug effects; Biological Transport - physiology; Body Fluids - secretion; Bumetanide - pharmacology; Chlorides - pharmacokinetics; Colforsin - pharmacology; Diuretics - pharmacology; Guinea Pigs; Hydrogen-Ion Concentration; Male; Mice; Mice, Inbred Strains; Models, Biological; Pancreatic Ducts - drug effects; Pancreatic Ducts - physiology; Pancreatic Ducts - secretion; Rats; Rats, Wistar; Research Papers; Secretin - pharmacology; Sodium Potassium Chloride Symporter Inhibitors; Solute Carrier Family 12, Member 2
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2004.061762

Fluid secretion by interlobular pancreatic ducts was determined by using video microscopy to measure the rate of swelling of isolated duct segments that had sealed following overnight culture. The aim was to compare the HCO 3 − requirement for secretin-evoked secretion in mouse, rat and guinea-pig pancreas. In mouse and rat ducts, fluid secretion could be evoked by 10 n m secretin and 5 μ m forskolin in the absence of extracellular HCO 3 − . In guinea-pig ducts, however, fluid secretion was totally dependent on HCO 3 − . Forskolin-stimulated fluid secretion by mouse and rat ducts in the absence of HCO 3 − was dependent on extracellular Cl − and was completely inhibited by bumetanide (30 μ m ). It was therefore probably mediated by a basolateral Na + –K + –2Cl − cotransporter. In the presence of HCO 3 − , forskolin-stimulated fluid secretion was reduced ∼40% by bumetanide, ∼50% by inhibitors of basolateral HCO 3 − uptake (3 μ m EIPA and 500 μ m H 2 DIDS), and was totally abolished by simultaneous application of all three inhibitors. We conclude that the driving force for secretin-evoked fluid secretion by mouse and rat ducts is provided by parallel basolateral mechanisms: Na + –H + exchange and Na + –HCO 3 − cotransport mediating HCO 3 − uptake, and Na + –K + –2Cl − cotransport mediating Cl − uptake. The absence or inactivity of the Cl − uptake pathway in the guinea-pig pancreatic ducts may help to account for the much higher concentrations of HCO 3 − secreted in this species.