ZENECA ZD6169 ACTIVATES ATP-SENSITIVE K-BLADDER OF THE GUINEA-PIG( CHANNELS IN THE URINARY)

The effects of Zeneca ZD6169, a tertiary carbinol, and levcromakalim w ere examined on the membrane potential of intact smooth muscle cells, and on ATP-sensitive K+ (K-ATP) channel currents in isolated smooth mu scle cells from the guinea pig urinary bladder. ZD6169 and levcromakal im induced a glibenclamide-sensitive hyperpolarization of the membrane potential, The ZD6169- and levcromakalim-induced K-ATP currents were half-maximal at 1.02 and 2.63 mu mol/l, respectively, with Hill coeffi cients of 1.46 and 1.62, respectively, The ZD6169-induced K-ATP curren ts were inhibited by internal ATP (3.0 mmol/l), reduced 34% by activat ors of protein kinase C, and decreased 35% when the external pH was lo wered to 6.4. This study provides the first characterization of ZD6169 on K-ATP currents and indicates that ZD6169 is a potent opener of K-A TP channels in the smooth muscle from the urinary bladder.