Concurrent and independent HCO3- and Cl- secretion in a human pancreatic duct cell line (CAPAN-1)
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AbstractThe present study investigated both HCO3- and Cl- secretions in a human pancreatic duct cell line, CA-PAN-1 using the short-circuit current (I-sc) technique. In Cl-/HCO3--containing solution, secretion (1 mu M) or forskolin (10 mu M) stimulated a biphasic rise in the I-sc which initially reached a peak level at about 3 min and then decayed to a plateau level after 7 min. Removal of external Cl- abolished the initial transient phase in the forskolin-induced I-sc while the plateau remained. In HCO3-/CO2-free solution, on the contrary, only the initial transient increase in I-sc was prominent. Summation of the current magnitudes observed in Cl--free and HCO3--free solutions over a time course of 10 min gave rise to a curve which was similar, both in magnitude and kinetics, to the current observed in Cl-/HCO3--containing solution. Removal of external Na+ greatly reduced the initial transient rise in the forskolin-induced I-sc response, and the plateau level observed under this condition was similar to that obtained in Cl--free solution, suggesting that Cl--dependent I-sc was also Na+-dependent. Bumetanide (50 mu M), an inhibitor of the Na+-K+-2Cl(-) cotransporter, and Ba2+ (1 mM), a K+ channel blocker, could reduce the forskolin-induced I-sc obtained in Cl-/HCO3--containing or HCO3--free solution. However, they were found to be ineffective when external Cl- was removed, indicating the involvement of these mechanisms in Cl- secretion. On the contrary, the HCO3--dependent (in the absence of external Cl-) forskolin-induced I-sc could be significantly reduced by carbonic anhydrase inhibitor, acetazolamide (45 mu M). Basolateral application of amiloride (100 mu M) inhibited the I-sc; however, a specific Na+-H+ exchanger blocker, 5-N-methyl-N-isobutylamiloride (MIA, 5-10 mu m) was found to be ineffective, excluding the involvement of the Na+-H+ exchanger. However, an inhibitor of H+-ATPase, N-ethylmaleimide did suppress the I-sc (IC50 = 22 mu M). Immunohistochemical studies also confirmed the presence of a vacuolar type of H+-ATPase in these cells. H2DIDS (100 mu M), an inhibitor of Na+- HCO3- cotransporter, was without effect. Apical addition of Cl- channel blocker, diphenylamine-2,2'-dicarboxylic acid (DPC, 1 mM), but not disulfonic acids, DLDS (100 mu m) or SITS (100 mu M), exerted an inhibitory effect on both CT and HCO3--dependent forskolin-induced I-sc responses. Histochemical studies showed discrete stainings of carbonic anhydrase in the monolayer of CA-PAN-1 cells, suggesting that HCO3- secretion may be specialized to a certain population of cells. The present results suggest that both HCO3- and Cl- secretion by the human pancreatic duct cells may occur concurrently and independently.
All Author(s) ListCheng HS, Leung PY, Chew SBC, Leung PS, Lam SY, Wong WS, Wang ZD, Chan HC
Journal nameJournal of Membrane Biology
Volume Number164
Issue Number2
Pages155 - 167
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesBiochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Cell Biology; CELL BIOLOGY; Physiology; PHYSIOLOGY

Last updated on 2021-21-01 at 01:17