Bicarbonate transport by the human pancreatic ductal cell line hpaf

Irma Demeter, Orsolya Hegyesi, Ákos Károly Nagy, Maynard R. Case, Martin C. Steward, Gábor Varga, Beáta Burghardt

    Research output: Contribution to journalArticlepeer-review

    Abstract

    OBJECTIVES:: The human pancreatic duct cell line, HPAF, has been shown previously to secrete Cl in response to Ca-mobilizing stimuli. Our aim was to assess the capacity of HPAF cells to transport and secrete HCO3. METHODS:: HPAF cells were grown as confluent monolayers on permeable supports. Short-circuit current was measured by voltage clamp. Intracellular pH (pHi) was measured by microfluorometry in cells loaded with 2′,7′-bis(2-carboxyethyl)-5(6) -carboxyfluorescein (BCECF). RESULTS:: In HCO3-free solutions, ATP-evoked changes in short-circuit current were inhibited by bumetanide, and the recovery of pHi from acid loading was abolished by 5-(N-ethyl-N-isopropyl)-amiloride (EIPA). In the presence of HCO3, ATP-evoked secretion was no longer inhibited by bumetanide, and there was a strong EIPA-insensitive recovery from acid loading, which was inhibited by 4,4′-diisothiocyanatodihydrostilbene-2,2′- disulfonate (H2DIDS). ATP, but not forskolin, stimulated HCO3 efflux from the cells. CONCLUSIONS:: In the absence of HCO3, ATP-evoked Cl secretion is driven by a basolateral Na-K-2Cl cotransporter, and pHi is regulated by apical and basolateral Na/H exchangers. In the presence of HCO3, ATP-evoked secretion is sustained in the absence of Na-K-2Cl cotransporter activity and is probably driven by basolateral Na-HCO3 cotransport. Copyright © 2009 by Lippincott Williams & Wilkins.
    Original languageEnglish
    Pages (from-to)913-920
    Number of pages7
    JournalPancreas
    Volume38
    Issue number8
    DOIs
    Publication statusPublished - Nov 2009

    Keywords

    • Bicarbonate transport
    • CaCC
    • CFTR
    • Intracellular pH
    • Pancreatic duct

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