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

The influence of endothelium-derived nitric oxide (EDNO) on relaxation induced by the nitrovasodilators, sodium nitroprusside and sodium nitrite was assessed in phenylephrine-stimulated hamster thoracic aortas, a preparation that displays significant basal release of EDNO. Removal of the endothelium or treatment with the NO synthase inhibitors, NG-nitro-L-arginine (L-NAG, 10-30 microM) or NG-methyl-L-arginine (L-NMMA; 100 microM) increased the potency and, except for sodium nitroprusside in endothelium-denuded segments, also increased the efficacy of the nitrovasodilators. Removal of the endothelium had no effect on relaxations induced by isoproterenol, an indication that these effects were specific for the nitrovasodilators. Removal of the endothelium, treatment of endothelium-intact preparations with L-NAG or L-NMMA, or exposure of these vessels to the guanylate cyclase inhibitor, methylene blue (10 microM) increased reactivity of the aortas to the guanosine 3':5'-cyclic monophosphate (cGMP) analogue, 8-Br cGMP. Measurement of cGMP revealed that endothelium-intact segments had a 6.5 fold higher level of cGMP than endothelium-denuded preparations and that sodium nitroprusside increased cGMP in both preparations by similar amounts in a concentration-dependent fashion. Exposure of endothelium-denuded or L-NAG-treated segments to sodium nitroprusside, to mimic the effects of basally released EDNO, depressed sodium nitrite and 8-Br cGMP reactivity in a manner similar to endothelium-intact segments. These data indicate that EDNO increases cGMP levels in vascular smooth muscle and that the elevated cGMP levels depress nitrovasodilator and 8-Br cGMP reactivities.
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PMID:Elevated guanosine 3':5'-cyclic monophosphate mediates the depression of nitrovasodilator reactivity in endothelium-intact blood vessels. 166 Jan 5

This study aimed to examine the direct influence of native endothelium derived relaxing factor (EDRF) on renin secretion. To this end isolated mouse renal juxtaglomerular cells were cocultured with bovine aortic endothelial cells which produced and released significant amounts of EDRF as assayed by guanylate cyclase activities which were measured separately in endothelial and juxtaglomerular cells as well as in the cocultures of juxtaglomerular with endothelial cells. EDRF production was blunted in the absence of extracellular L-arginine and in the presence of N omega-nitro-L-arginine (L-NAG; 200 microM). Inhibition of endothelial EDRF production by removal of arginine or addition of L-NAG was associated with a significant decrease of renin secretion from the cocultures while the same regimen had no effect on renin secretion from JG cells alone. Exogenous generation of nitric oxide by the addition of sodium nitroprusside (100 microM) stimulated renin secretion in the cocultures both at normal and inhibited EDRF formation as well as from juxtaglomerular cells alone. These findings suggest that native EDRF released from vascular endothelial cells is a stimulatory signal for renin secretion from renal juxtaglomerular cells.
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PMID:Effect of endothelium-derived relaxing factor on renin secretion from isolated mouse renal juxtaglomerular cells. 790 75

The cytosolic calcium level ([Ca2+]i) and the membrane-bound guanylyl cyclase activity in the isolated rat intestinal epithelial cells were investigated. Heat-stable enterotoxin of Vibrio cholerae non-01 (NAG-ST) was found to increase both the [Ca2+]i and the enzyme activity. These changes occur similarly until 5 min of incubation with NAG-ST, indicating that these changes might be involved in NAG-ST induced signal transduction in rat enterocytes.
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PMID:Rise of cytosolic Ca2+ and activation of membrane-bound guanylyl cyclase activity in rat enterocytes by heat-stable enterotoxin of Vibrio cholerae non-01. 949 23

This study was undertaken to find out the mechanism of non-agglutinable Vibrio cholerae heat-stable enterotoxin (NAG-ST)-induced calcium influx across the plasma membrane. Adriamycin, an inhibitor of IP3-specific 3-kinase, could not inhibit NAG-ST-induced calcium influx in rat intestinal epithelial cells, which suggested that inositol 1,3,4,5-tetrakisphosphate (IP4) had no role in NAG-ST-induced calcium influx. NAG-ST increased intracellular nitric oxide level of rat enterocytes as measured by a fluorimetric method using a fluoroprobe 4,5-diaminofluorescein-2-diacetate (DAF-2DA). N-Nitro-L-arginine, an inhibitor of nitric oxide synthase, inhibited NAG-ST-induced rise in nitric oxide level and also calcium influx. Inhibition of inositol trisphosphate (IP3)-mediated intracellular calcium mobilization by Dantrolene could also inhibit NAG-ST-induced rise in intracellular nitric oxide level. Moreover, inhibition of soluble guanylate cyclase by inhibitors (ODQ, LY83583) could inhibit the NAG-ST-induced rise in cyclic guanosine-3',5'-monophosphate (cGMP) level and calcium influx. From this study, it is evident that NAG-ST causes IP3-mediated calcium release from intracellular calcium store, which then stimulates nitric oxide production by activating nitric oxide synthase and the nitric oxide through cGMP activates calcium influx.
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PMID:Role of nitric oxide in NAG-ST induced store-operated calcium entry in rat intestinal epithelial cells. 1529 24