Vectorial Bicarbonate Transport by Capan-1 Cells: a Model for Human Pancreatic Ductal Secretion.

Human pancreatic ducts secrete a bicarbonate-rich fluid but our knowledge of the secretory process is based mainly on studies of animal models. Our aim was to determine whether the HCO₃^- transport mechanisms in a human ductal cell line are similar to those previously identified in guinea-pig pancreatic ducts. Intracellular pH was measured by microfluorometry in Capan-1 cell monolayers grown on permeable filters and loaded with BCECF. Epithelial polarization was assessed by immunolocalization of occludin. Expression of mRNA for key electrolyte transporters and receptors was evaluated by RT-PCR. Capan-1 cells grown on permeable supports formed confluent, polarized monolayers with well developed tight junctions. The recovery of pH_i from an acid load, induced by a short NH₄⁺ pulse, was mediated by Na⁺-dependent transporters located exclusively at the basolateral membrane. One was independent of HCO₃^- and blocked by EIPA (probably NHE1) while the other was HCO₃^--dependent and blocked by H₂DIDS (probably pNBC1). Changes in pH_i following blockade of basolateral HCO₃^- accumulation confirmed that the cells achieve vectorial HCO₃^- secretion. Dose-dependent increases in HCO₃^- secretion were observed in response to stimulation of both secretin and VPAC receptors. ATP and UTP applied to the apical membrane stimulated HCO₃^- secretion but were inhibitory when applied to the basolateral membrane. HCO₃^- secretion in guinea-pig ducts and Capan-1 cell monolayers share many common features, suggesting that the latter is an excellent model for studies of human pancreatic HCO₃^- secretion. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]