Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 492, Issue 1, Pages 13-19Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2004.03.057
Keywords
nitric oxide; K-ATP; c-GMP; PKG; urinary bladder
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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 muM) potentiated activation of an inward current in whole cell patch clamp experiments. Glibenclamide (10 muM) and IH[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 muM) inhibited the SIN-activated current. Both in cell-attached and in inside out patches, SIN (200 muM) potentiated K-ATP channel activity, and the increased channel activity in inside out patches was suppressed by glibenclamide (50 muM), ATP (1 mM) and (9s,10R,12R)-2,3,9,10,11,12-Hexahydro-10-methoxy-2,9-dimethyl-l-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 muM) increased the K-ATP channel activity in cell-attached patches, and this was suppressed by glibenclamide (50 muM). These results suggest that the NO-c-GMP-PKG pathway contributes to activation of K-ATP channels in guinea-pig urinary bladder myocytes. (C) 2004 Elsevier B.V. All rights reserved.
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