Zeneca ZD6169 activates ATP-sensitive K+ channels in the urinary bladder of the guinea pig

The effects of Zeneca ZD6169, a tertiary carbinol, and levcromakalim were examined on the membrane potential of intact smooth muscle cells, and on ATP-sensitive K+ (KATP) channel currents in isolated smooth muscle cells from the guinea pig urinary bladder. ZD6169 and levcromakalim induced a glibenclamide-sensitive hyperpolarization of the membrane potential. The ZD6169- and levcromakalim-induced KATP currents were half-maximal at 1.02 and 2.63 mumol/l, respectively, with Hill coefficients of 1.46 and 1.62, respectively. The ZD6169-induced KATP currents were inhibited by internal ATP (3.0 mmol/l), reduced 34% by activators of protein kinase C, and decreased 35% when the external pH was lowered to 6.4. This study provides the first characterization of ZD6169 on KATP currents and indicates that ZD6169 is a potent opener of KATP channels in the smooth muscle from the urinary bladder.