| Autor: |
Yunoki, Takakazu, Zhu, Hai-Lei, Iwasa, Kazuomi, Tomoda, Toshihisa, Aishima, Manami, Shibata, Atsushi, Naito, Seiji, Teramoto, Noriyoshi |
| Zdroj: |
Naunyn-Schmiedeberg's Archives of Pharmacology; Jan2008, Vol. 376 Issue 5, p309-319, 11p, 1 Diagram, 8 Graphs |
| Abstrakt: |
The effects of ZD0947, a novel urinary bladder selective ATP-sensitive potassium channel (KATP channel) opener, on carbachol-induced contractions of isolated guinea pig urinary bladder strips were investigated to compare its ability to relax norepinephrine-induced contraction of the aorta. Electrophysiological techniques were also utilized to compare the effects of ZD0947 on membrane currents between guinea pig detrusor and aortic myocytes. ZD0947 caused a significant reduction of the carbachol-induced contractile activity, demonstrating a biphasic relaxation (the first and second components). Although glibenclamide antagonized the effects of two components for the ZD0947-induced relaxation, gliclazide, a selective sulphonylurea receptor 1 (SUR1) antagonist, reduced the effects of the first component but not the second component of the ZD0947-induced relaxation. ZD0947 also reduced the norepinephrine-induced contraction of the aorta. ZD0947 reduced electrical excitability of detrusor smooth muscles, inhibiting spike discharges and also hyperpolarizing the membrane as measured with microelectrodes. In conventional whole-cell configuration, ZD0947 caused a glibenclamide-sensitive K+ current (i.e., KATP current) at a holding potential of −60 mV in guinea pig detrusor and aortic myocytes. The current density of ZD0947-induced KATP currents in guinea pig detrusor myocytes was significantly larger than that in aortic smooth muscle cells. These results show that ZD0947 caused a significant relaxation through the activation of KATP channels in detrusor muscle. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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