Article date: August 2001
By: Hai‐Tian Fan, Shigeru Morishima, Hajime Kida, Yasunobu Okada in Volume 133, Issue 7, pages 1096-1106
Some phenol derivatives are known to block volume‐sensitive Cl− channels. However, effects on the channel of the bisphenol phloretin, which is a known blocker of glucose uniport and anion antiport, have not been examined. In the present study, we investigated the effects of phloretin on volume‐sensitive Cl− channels in comparison with cyclic AMP‐activated CFTR Cl− channels and Ca2+‐activated Cl− channels using the whole‐cell patch‐clamp technique.
Extracellular application of phloretin (over 10 μM) voltage‐independently, and in a concentration‐dependent manner (IC50 ∼30 μM), inhibited the Cl− current activated by a hypotonic challenge in human epithelial T84, Intestine 407 cells and mouse mammary C127/CFTR cells.
In contrast, at 30 μM phloretin failed to inhibit cyclic AMP‐activated Cl− currents in T84 and C127/CFTR cells. Higher concentrations (over 100 μM) of phloretin, however, partially inhibited the CFTR Cl− currents in a voltage‐dependent manner.
At 30 and 300 μM, phloretin showed no inhibitory effect on Ca2+‐dependent Cl− currents induced by ionomycin in T84 cells.
It is concluded that phloretin preferentially blocks volume‐sensitive Cl− channels at low concentrations (below 100 μM) and also inhibits cyclic AMP‐activated Cl− channels at higher concentrations, whereas phloretin does not inhibit Ca2+‐activated Cl− channels in epithelial cells.
Some phenol derivatives are known to block volume‐sensitive Cl− channels. However, effects on the channel of the bisphenol phloretin, which is a known blocker of glucose uniport and anion antiport, have not been examined. In the present study, we investigated the effects of phloretin on volume‐sensitive Cl− channels in comparison with cyclic AMP‐activated CFTR Cl− channels and Ca2+‐activated Cl− channels using the whole‐cell patch‐clamp technique.
Extracellular application of phloretin (over 10 μM) voltage‐independently, and in a concentration‐dependent manner (IC50 ∼30 μM), inhibited the Cl− current activated by a hypotonic challenge in human epithelial T84, Intestine 407 cells and mouse mammary C127/CFTR cells.
In contrast, at 30 μM phloretin failed to inhibit cyclic AMP‐activated Cl− currents in T84 and C127/CFTR cells. Higher concentrations (over 100 μM) of phloretin, however, partially inhibited the CFTR Cl− currents in a voltage‐dependent manner.
At 30 and 300 μM, phloretin showed no inhibitory effect on Ca2+‐dependent Cl− currents induced by ionomycin in T84 cells.
It is concluded that phloretin preferentially blocks volume‐sensitive Cl− channels at low concentrations (below 100 μM) and also inhibits cyclic AMP‐activated Cl− channels at higher concentrations, whereas phloretin does not inhibit Ca2+‐activated Cl− channels in epithelial cells.
British Journal of Pharmacology (2001) 133, 1096–1106; doi:10.1038/sj.bjp.0704159
DOI: 10.1038/sj.bjp.0704159
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