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 effects of various spontaneous nitric oxide (NO) donors and NO synthase inhibitors on endothelin- production were examined using porcine cultured aortic endothelial cells. NO donors such as (+/-)-(E)-4-methyl-2-[(E)-hydroxyimino]-5-nitro-3-hexanamide (NOR 2), (+/-)-(E)-4-ethyl-2-[( E)-hydroxyimino]-5-nitro-3-hexanamide (NOR 3) and (+/-)-N-[(E)-4-ethyl-2-[(Z)-hydroxyimino]-5-nitro-3-hexen-1- yl]-3-pyridine carboxamide (NOR 4) suppressed effectively the release of endothelin-1 from the cells. Endothelin-1 mRNA expression was also attenuated by these compounds. Other NO donors such as 3-[2-hydroxy-1-(1-methylethyl)-2-nitrosohydrazino]-1-propanamin e (NOC 5), 2,2'-(hydroxynitrosohydrazino)bis-ethanamine (NOC 18), s-nitroso-n-acetyl-DL-penicillamine, N-morpholino sydnonimine (SIN-1) had no effects on endothelin-1 production. Endothelial intracellular cyclic guanosine monophosphate (cGMP) levels were significantly increased by all NO donors. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a selective soluble guanylyl cyclase inhibitor, had no effect on the NOR 3-induced decrease in endothelin-1 secretion, although cGMP production was abolished by ODQ. NOR 3 also inhibited endothelin-1 secretion even in the presence of 2-(4-carboxyphenyl)-4,4,5,5-tetrametylimidazole-1-oxyl 3-oxide (carboxy-PTIO), a NO scavenger. NOR 3-induced inhibitory effects on endothelin-1 secretion were abolished by preincubation of the compound in phosphate-buffered saline (37 degrees C, 4 h), a procedure by which about 98% of the parent compound's ability to release NO was lost. NO synthase inhibitors such as N(G)-nitro-L-arginine, N(G)-monomethyl-L-arginine and N(G)-nitro-L-arginine methyl ester (L-NAME) enhanced prepro endothelin-1 mRNA expression and significantly increased endothelin-1 release from endothelial cells. Endothelin-1 secretion was also increased effectively by carboxy-PTIO or ODQ. When the cells were exposed to L-NAME with carboxy-PTIO or ODQ, no significant further increase in endothelin-1 release was observed. These results suggest that endogenous NO inhibits endothelin-1 production through guanylyl cyclase/cGMP-dependent mechanisms. In contrast, it seems unlikely that exogenous NO has an inhibitory effect on endothelin-1 production in endothelial cells. NOR compounds inhibit endothelin-1 production perhaps through NO/cGMP-independent mechanisms, i.e., through an unknown effect of the parent compound itself.
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PMID:Effects of endogenous and exogenous nitric oxide on endothelin-1 production in cultured vascular endothelial cells. 992 Jan 86

We previously reported stimulatory effects of endogenous and exogenous nitric oxide (NO) on gastric acid secretion. In the present study, we investigated effects of NO donors on release of histamine, which is related to acid secretion, in isolated rat gastric mucosal cells. NO donors such as (+/-)-(E)-4-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexanamide (NOR 1) and sodium nitroprusside significantly augmented the histamine release. It was inhibited by 2-(4-carboxyphenyl)-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-amide (carboxy-PTIO), a NO scavenger, and 6-(phenylamino)-5,8-quinolinedione (LY83583), a soluble guanylate cyclase inhibitor. Dibutyryl cyclic GMP also stimulated histamine release. These results suggest that NO donors act on cyclic GMP pathway in isolated gastric mucosal cells, resulting in facilitation of histamine release. NO may stimulate gastric acid secretion through histamine release from the histamine-containing cells, possibly enterochromaffin-like cells.
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PMID:Stimulatory effects of nitric oxide donors on histamine release in isolated rat gastric mucosal cells. 1284 16