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.
Heppner
T J
TJ
Department of Pharmacology, University of Vermont, Colchester 05446, USA.
Bonev
A
A
Li
J H
JH
Kau
S T
ST
Nelson
M T
MT
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000577:Amides / Q000494:pharmacology*; D000818:Animals; D001577:Benzophenones / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects*; D011493:Protein Kinase C / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology
D000577:Amides; D001577:Benzophenones; D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; C095007:Zeneca ZD 6169; D019806:Cromakalim; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D005905:Glyburide