Cytochrome P450 inhibitors attenuate the hypotonic shock-induced increases in K+ efflux in LLC-PK1 cells

Cell volume regulation in LLC-PK1 cells was evaluated by measuring 86Rb efflux (rate constant), used as an indicator of K+ efflux. Hypotonic shock induced a transient increase in the rate constant which returned to baseline values after 15 min. ETYA, an arachidonic acid-competitive antagonist as well as the cytochrome P450 inhibitors SKF 525-A, clotrimazole and 7-ethoxyresorufin, inhibited the hypotonic shock-induced increment in the rate constant. Arachidonic acid did not change hypotonic shock-induced increments in K+ efflux. LLC-PK1 cells were unable to metabolize 14C-arachidonic acid. We concluded that although arachidonic acid inhibitors block the hypotonic shock-induced increment in K+ efflux, this effect cannot be related to inhibition of arachidonic acid metabolism.