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Chloride transport in microperfused interlobular ducts isolated from guinea‐pig pancreas
Author(s) -
Ishiguro H.,
Naruse S.,
Kitagawa M.,
Mabuchi T.,
Kondo T.,
Hayakawa T.,
Case R. M.,
Steward M. C.
Publication year - 2002
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2001.012490
Subject(s) - forskolin , chemistry , stimulation , medicine , ion transporter , endocrinology , chloride channel , chloride , cotransporter , guinea pig , cystic fibrosis transmembrane conductance regulator , secretin , epithelial polarity , intracellular , lumen (anatomy) , biophysics , secretion , biochemistry , biology , sodium , membrane , organic chemistry , gene
Isolated interlobular ducts from the guinea‐pig pancreas secrete a HCO 3 − ‐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 HCO 3 − and was not inhibited by application of the anion channel/transporter inhibitor H 2 DIDS 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 HCO 3 − and was inhibited by basolateral H 2 DIDS. It is therefore mediated mainly by Cl − /HCO 3 − exchange. With high Cl − and low HCO 3 − 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 HCO 3 − 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 HCO 3 − secretion via anion conductances in the luminal membrane, possibly CFTR.