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Zeneca ZD6169 activates ATP-sensitive K+ channels in the urinary bladder of the guinea pig.
Heppner T, Bonev A, Li J, Kau S, Nelson MT
Pharmacology. 1996;53( 3):170-9.
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Abstract
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.
Keyword(s)
Animals; Cromakalim; Dose-Response Relationship, Drug; Enzyme Activation; Guinea Pigs; Hydrogen-Ion Concentration; Ion Channel Gating; drug effects: Membrane Potentials; drug effects: Muscle, Smooth; drug effects: Potassium Channels; drug effects: Urinary Bladder; metabolism: Protein Kinase C; pharmacology: Adenosine Triphosphate; pharmacology: Amides; pharmacology: Benzophenones; pharmacology: Benzopyrans; pharmacology: Glyburide; pharmacology: Pyrroles