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1 Departamento de Fisiología y Farmacología, Universidad de Salamanca, 37007 Salamanca, Spain2 School of Biological Sciences, University of Manchester, Manchester M13 9PT, UK
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 HCO3 requirement for secretin-evoked secretion in mouse, rat and guinea-pig pancreas. In mouse and rat ducts, fluid secretion could be evoked by 10 nM secretin and 5 µM forskolin in the absence of extracellular HCO3. In guinea-pig ducts, however, fluid secretion was totally dependent on HCO3. Forskolin-stimulated fluid secretion by mouse and rat ducts in the absence of HCO3 was dependent on extracellular Cl and was completely inhibited by bumetanide (30 µM). It was therefore probably mediated by a basolateral Na+K+2Cl cotransporter. In the presence of HCO3, forskolin-stimulated fluid secretion was reduced
40% by bumetanide,
50% by inhibitors of basolateral HCO3 uptake (3 µM EIPA and 500 µM H2DIDS), 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+HCO3 cotransport mediating HCO3 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 HCO3 secreted in this species.
(Received 22 January 2004;
accepted after revision 12 February 2004;
first published online 20 February 2004)
Corresponding author J. I. San Román: Departamento de Fisiología y Farmacología, Universidad de Salamanca, Edificio Departamental, Campus Miguel de Unamuno, 37007 Salamanca, Spain. Email: nachosr{at}usal.es
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