TY - JOUR
T1 - Endogenous arachidonic acid inhibits hypotonically-activated Cl- channels in isolated rat hepatocytes
AU - Sakai, Hideki
AU - Kakinoki, Bunpei
AU - Diener, Martin
AU - Takeguchi, Noriaki
PY - 1996/8
Y1 - 1996/8
N2 - Properties of hypotonically-activated Cl- channels in isolated rat hepatocytes were studied by the patch-clamp whole-cell technique. Hypotonic stress (140-150 mosmol kg-1 H2O) induced a hyperpolarization of the membrane of hepatocytes in the presence of an inwardly oriented Cl- gradient, but had no effect on the membrane potential in the absence of Cl-. An increase in the hypotonically-induced conductance was significantly inhibited by 4-acetamido-4'isothiocyanatostilbene-2,2'-disulfonic,2'-disulfonic acid (SITS; 50 μM), but not by Ba2+ (1 mM). Pre-incubation with arachidonic acid (20 μM) significantly inhibited the hypotonically-activated conductance. The combined application of a cyclo-oxygenase inhibitor, indomethacin (50 μM) and a lipoxygenase inhibitor, esculetin (100 μM) also inhibited the conductance, whereas quinacrine (200 μM), a phospholipase A2 inhibitor, significantly induced a large steady conductance. Outward Cl- currents, but not cationic currents, were elicited by the hypotonic stress. The current did not show any rapid time-dependent inactivation during the voltage clamp of 0.1 s. The combined application of arachidonic acid, indomethacin and esculetin inhibited the hypotonically-activated Cl- currents. The present study has shown that the Cl- channel is activated by exposure to hypotonic stress and closed by an increase in arachidonic acid concentration in isolated rat hepatocytes.
AB - Properties of hypotonically-activated Cl- channels in isolated rat hepatocytes were studied by the patch-clamp whole-cell technique. Hypotonic stress (140-150 mosmol kg-1 H2O) induced a hyperpolarization of the membrane of hepatocytes in the presence of an inwardly oriented Cl- gradient, but had no effect on the membrane potential in the absence of Cl-. An increase in the hypotonically-induced conductance was significantly inhibited by 4-acetamido-4'isothiocyanatostilbene-2,2'-disulfonic,2'-disulfonic acid (SITS; 50 μM), but not by Ba2+ (1 mM). Pre-incubation with arachidonic acid (20 μM) significantly inhibited the hypotonically-activated conductance. The combined application of a cyclo-oxygenase inhibitor, indomethacin (50 μM) and a lipoxygenase inhibitor, esculetin (100 μM) also inhibited the conductance, whereas quinacrine (200 μM), a phospholipase A2 inhibitor, significantly induced a large steady conductance. Outward Cl- currents, but not cationic currents, were elicited by the hypotonic stress. The current did not show any rapid time-dependent inactivation during the voltage clamp of 0.1 s. The combined application of arachidonic acid, indomethacin and esculetin inhibited the hypotonically-activated Cl- currents. The present study has shown that the Cl- channel is activated by exposure to hypotonic stress and closed by an increase in arachidonic acid concentration in isolated rat hepatocytes.
KW - Arachidonic acid
KW - Cl channel
KW - Rat hepatocyte
UR - http://www.scopus.com/inward/record.url?scp=0029909949&partnerID=8YFLogxK
U2 - 10.2170/jjphysiol.46.311
DO - 10.2170/jjphysiol.46.311
M3 - 学術論文
C2 - 8988440
AN - SCOPUS:0029909949
SN - 0021-521X
VL - 46
SP - 311
EP - 318
JO - Japanese Journal of Physiology
JF - Japanese Journal of Physiology
IS - 4
ER -