Nitric oxide activates glibenclamide-sensitive K⁺ channels in urinary bladder myocytes through a c-GMP-dependent mechanism

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• 作者：Deka ; Dilip K. ; Brading ; Alison F.
• 关键词：Nitric oxide ; K_ATP ; c-GMP ; PKG ; Urinary bladder
• 刊名：European Journal of Pharmacology
• 出版年：2004
• 出版时间：May 10, 2004
• 年：2004
• 卷：492
• 期：1
• 页码：13-19
• 全文大小：400 K

文摘

In the present investigation, we used standard patch clamp techniques to test whether nitric oxide (NO) generation has any role to play with either activation or inhibition of ATP-sensitive (K_ATP) channels in guinea-pig urinary bladder. We found that NO generation leads to activation of K_ATP channels through a cyclic guanosine monophosphate (c-GMP)-dependent protein kinase. 3-Morpholinosydnonimine (SIN, 100 μM) potentiated activation of an inward current in whole cell patch clamp experiments. Glibenclamide (10 μM) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 μM) inhibited the SIN-activated current. Both in cell-attached and in inside out patches, SIN (200 μM) potentiated K_ATP channel activity, and the increased channel activity in inside out patches was suppressed by glibenclamide (50 μM), ATP (1 mM) and (9s,10R,12R)-2,3,9,10,11,12-Hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12,-epoxy-1H-diindolo[1,2,3-fg:3′,2′,1′-kl]pyrrolo[3,4-i][1,6] benzodiazocine-10-carboxylic acid, methyl ester (KT-5823, 10 nM). 8-Br-cGMP (100 μM) increased the K_ATP channel activity in cell-attached patches, and this was suppressed by glibenclamide (50 μM). These results suggest that the NO-c-GMP-PKG pathway contributes to activation of K_ATP channels in guinea-pig urinary bladder myocytes.