title: Chloride transport in microperfused interlobular ducts isolated from guinea-pig pancreas.
abstract: Isolated interlobular ducts from the guinea-pig pancreas secrete a HCO3--rich fluid in response to secretin. To determine the role of Cl- transporters in this process, intracellular Cl- concentration ([Cl-]i) was measured in ducts loaded with the Cl--sensitive fluoroprobe, 6-methoxy-N-ethylquinolinium chloride (MEQ). [Cl-]i decreased when the luminal Cl- concentration was reduced. This effect was stimulated by forskolin, was not dependent on HCO3- and was not inhibited by application of the anion channel/transporter inhibitor H2DIDS to the luminal membrane. It is therefore attributed to a cAMP-stimulated Cl- conductance, probably the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel. [Cl-]i also decreased when the basolateral Cl- concentration was reduced. This effect was not stimulated by forskolin, was largely dependent on HCO3- and was inhibited by basolateral H2DIDS. It is therefore mediated mainly by Cl-/HCO3- exchange. With high Cl- and low HCO3- concentrations in the lumen, steady-state [Cl-]i was 25-35 mM in unstimulated cells. Stimulation with forskolin caused [Cl-]i to increase by approximately 4 mM due to activation of the luminal anion exchanger. With low Cl- and high HCO3- concentrations in the lumen to simulate physiological conditions, steady-state [Cl-]i was 10-15 mM in unstimulated cells. Upon stimulation with forskolin, [Cl-]i fell to approximately 7 mM due to increased Cl- efflux via the luminal conductance. We conclude that, during stimulation under physiological conditions, [Cl-]i decreases to very low levels in guinea-pig pancreatic duct cells, largely as a result of the limited capacity of the basolateral transporters for Cl- uptake. The resulting lack of competition from intracellular Cl- may therefore favour HCO3- secretion via anion conductances in the luminal membrane, possibly CFTR.
authors.affiliation: Internal Medicine II and Human Nutrition, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466 8550, Japan. ishiguro@htc.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: T
authors.initials: T
authors.lastname: Mabuchi
authors.forename: T
authors.initials: T
authors.lastname: Kondo
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: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002712:Chlorides / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D006706:Homeostasis; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D009994:Osmolar Concentration; D010183:Pancreatic Ducts / Q000187:drug effects / Q000378:metabolism*; D010477:Perfusion
chemical_list: D002712:Chlorides; C018564:dihydro-DIDS; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid