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- Title
Chloride transport in microperfused interlobular ducts isolated from guinea-pig pancreas.
- Authors
Ishiguro, H.; Naruse, S.; Kitagawa, M.; Mabuchi, T.; Kondo, T.; Hayakawa, T.; Case, R. M.; Steward, M. C.
- 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 m m in unstimulated cells. Stimulation with forskolin caused [ Cl−]i to increase by approximately 4 m m 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 m m in unstimulated cells. Upon stimulation with forskolin, [ Cl−]i fell to approximately 7 m m 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.
- Publication
Journal of Physiology, 2002, Vol 539, Issue 1, p175
- ISSN
0022-3751
- Publication type
Article
- DOI
10.1113/jphysiol.2001.012490