Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relaxant effects of the K+ channel openers, NIP-121, (+)-7,8-dihydro-6,6-dimethyl-7-hydroxy-8-(2-oxo-piperidin-1-yl)-6H - pyrano[2,3-f]benz-2,1,3-oxadiazole, and cromakalim, were investigated in epithelium-intact and -denuded tracheal spirals isolated from guinea-pigs. In the presence of 5 microM indomethacin, NIP-121 (0.01-1 microM) and cromakalim (0.1-10 microM) relaxed, in a concentration-dependent manner, epithelium-intact and -denuded trachea precontracted with a thromboxane A2 mimetic, U46619, 9,11-dideoxy-9 alpha, 11 alpha-methanoepoxy-prostaglandin F2 alpha (30 nM). The relaxations of epithelium-denuded trachea were significantly decreased as compared with those of epithelium-intact trachea. The relaxations induced by salbutamol or aminophylline were not affected by epithelium removal. In epithelium-intact trachea, the NIP-121- and cromakalim-induced relaxations were not modulated by the neutral endopeptidase inhibitor, phosphoramidon (10 microM), or the nitric oxide synthesis inhibitor, N omega-nitro-L-arginine (100 microM). However, the guanylate cyclase inhibitor, methylene blue (100 microM), significantly reduced NIP-121- and cromakalim-induced relaxation of epithelium-intact trachea. Methylene blue also reduced sodium nitroprusside-induced relaxation but did not affect isoprenaline-induced relaxation. These findings suggest that the K+ channel openers, NIP-121 and cromakalim, may induce, at least in part, epithelium-dependent and methylene blue-sensitive relaxation of the guinea-pig isolated trachea.
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PMID:K+ channel openers produce epithelium-dependent relaxation of the guinea-pig trachea. 749 76

The role of L-type Ca(2+) channels in the relaxation to nitric oxide (NO)-mediated MaxiK(Ca) channel activation was examined in guinea pig aorta. Acetylcholine (ACh) produced an endothelium-dependent relaxation of guinea pig aorta precontracted with noradrenaline (NA), which was abolished by an NO synthase inhibitor, N(G)-nitro-L-arginine (L-NNA). Both endothelium-dependent relaxation by ACh and endothelium-independent relaxation by an NO donor, (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide (NOR3), were strongly suppressed by a soluble guanylate cyclase (sGC) inhibitor, 1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one (ODQ), suggesting that increased intracellular cGMP plays the key role in both responses. ACh- and NOR3-induced relaxations were significantly suppressed by iberiotoxin (IbTX), a selective blocker of MaxiK(Ca) channels. ACh- and NOR3-induced relaxations were greatly attenuated when arteries were precontracted with high KCl instead of NA, supporting the idea that K(+) channel activation mediates the relaxant responses. (6) NOR3-induced relaxations were not affected by a L-type Ca(2+) channel blocker, diltiazem. Furthermore, endothelium-independent relaxation by a K(ATP) channel opener, (+)-7,8-dihydro-6, 6-dimethyl-7-hydroxy-8-(2-oxo-1-piperidinyl)-6H-pyrano[2,3-f] benz-2,1, 3-oxadiazole (NIP-121) was not affected by diltiazem and nicardipine. These findings suggest that blockade of L-type Ca(2+) channels is not a major mechanism responsible for the vascular relaxation due to NO-mediated MaxiK(Ca) channel activation in guinea pig aorta.
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PMID:NO-mediated MaxiK(Ca) channel activation produces relaxation of guinea pig aorta independently of voltage-dependent L-type Ca(2+) channels. 1112 Mar 77