Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Nitric oxide (NO) is shown to be synthesized in the central nervous system as well as in vascular endothelial cells. However, the physiological role of NO in cardiovascular regulation in the central nervous system remains unclear. The present study examines whether NO plays a role in the regulation of neuronal activity in the nucleus tractus solitarius (NTS). Single-unit extracellular recordings were obtained from NTS neurons in slices (400 microns) of the rat brainstem, which had spontaneous discharges at a frequency of 0.5 to 3 spikes per second. Eighty-one neurons were tested for sensitivity to L-arginine, which is the physiological precursor of NO. L-Arginine (10(-7) to 10(-4) mol/L) increased neuronal activity dose dependently in 33 (40.7%) of 81 neurons tested, but D-arginine (10(-5) mol/L) did not. The neurons that responded to L-arginine responded to glutamate as well. NG-Monomethyl-L-arginine (10(-5) to 3 x 10(-5) mol/L), an inhibitor of the formation of NO, dose-dependently blocked increases in the neuronal activity evoked with L-arginine (10(-5) mol/L). Hemoglobin (1.5 mg/L), a trapper of NO, and methylene blue (10(-5) mol/L), an inhibitor of guanylate cyclase, also blocked increases in the neuronal activity evoked with L-arginine (10(-5) mol/L). Sodium nitroprusside (SNP, 10(-5) to 10(-4) mol/L), which spontaneously produces NO, increased the neuronal activity in the neurons that responded to L-arginine. SNP did not alter the neuronal activity of the neurons that did not respond to L-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitric oxide influences neuronal activity in the nucleus tractus solitarius of rat brainstem slices. 801 84

Sodium nitroprusside spontaneously breaks down in solution to produce the vasodilator nitric oxide. In many cell types, this stimulates the cytosolic form of the enzyme guanylate cyclase, resulting in the elevation of cyclic GMP (cGMP). We have investigated the effect of sodium nitroprusside on the generation of cGMP in primary human thyrocytes and the SV40-transfected human thyroid cell line SGHTL-189. A dose-dependent increase in cGMP was obtained and the maximum response was observed with concentrations above 10 microM sodium nitroprusside in both cell types. Methylene blue (50 microM) had no significant effect on basal cGMP production but inhibited the effect of sodium nitroprusside at all concentrations tested, thus demonstrating that the effect was due to nitric oxide. Sodium nitroprusside had no effect on cyclic AMP (cAMP) production in these cells. TSH at 100 and 1000 microU/ml significantly stimulated the production of cAMP, but not that of cGMP, in primary human thyrocytes. Sodium nitroprusside had no significant effect on basal or TSH-stimulated triiodothyronine secretion in primary human thyrocytes. Forskolin (10 microM) significantly stimulated cAMP production in both primary thyrocytes and SGHTL-189 cells. Although forskolin had no significant effect on basal cGMP production, sodium nitroprusside-stimulated cGMP production was significantly reduced by forskolin. However, this inhibitory effect was not related to the production of cAMP.
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PMID:Nitric oxide stimulates cyclic GMP in human thyrocytes. 809 15

The intracellular content of cyclic GMP (cGMP) is known to mediate the effects of various vasodilating substances on glomerular mesangial cells. However, little is known about the role of soluble guanylate cyclase (SGC) in these cells in diabetes. We, therefore, investigated the changes in SGC activity as well as the cGMP content in rat mesangial cells (MC) cultured under high glucose or hypertonic conditions. The following results were obtained. 1. Sodium nitroprusside (SNP) (10(-4) M, 10min.) increased cyclic GMP (cGMP) content in MC from 8.17 +/- 0.99 pmol/mg protein to 981.6 +/- 86.3. 2. SNP (10(-4) M) stimulated SGC activity from 38.3 +/- 10.8 pmol cGMP formed/mg protein/10 minutes to 74.4 +/- 5.2. 3. In the coincubation experiment with bovine aortic endothelial cells, bradykinin (10(-6) M, 10min.) increased cGMP content in MC from 6.24 +/- 1.35 to 348.3 +/- 45.3. However, 4. the activity of SGC and SNP-induced increase of cGMP were not influenced by culturing MC in high glucose or hypertonic media. Similarly, the cGMP increase in MC coincubated with BAEC under bradykinin stimulation was not altered by culturing under high glucose or hypertonic conditions. These data suggested that SGC may play an important role in the regulation of cGMP content in MC. However, this enzyme may not be involved in the increase of cGMP content in MC cultured under high glucose condition.
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PMID:[Effect of glucose on soluble guanylate cyclase in cultured rat mesangial cells]. 810 Feb 85

A diminished relaxant response of atherosclerotic arteries to nitrovasodilators has been frequently observed in advanced stages of hypercholesterolemia. In the present study, we investigated whether this effect might be a result of reduced activity of smooth muscle guanylyl cyclase. Experimental atherosclerosis was induced by feeding rabbits a cholesterol-rich diet (1%) over a period of 4 months. Aortas were removed and homogenized, and guanylyl cyclase activity was measured in the 100,000 g supernatants. Sodium nitroprusside, which stimulated cyclic GMP (cGMP) formation in control tissues almost 200-fold (from 3 to 585 pmol cGMP.mg-1 x min-1), increased enzyme activities in atherosclerotic aortas only approximately 90-fold (from 3 to 257 pmol cGMP.mg-1 x min-1). Similarly, the maximal stimulatory effects of S-nitroso-glutathione were reduced from 200-fold (controls) to 114-fold in atherosclerotic tissues. Basal guanylyl cyclase activities were identical in both atherosclerotic and control vessels. Hypercholesterolemia also reduced the activity of smooth muscle adenylyl cyclase. In control aortas, basal and NaF-stimulated enzyme activities were 24 and 349 pmol cAMP.mg-1 x min-1, respectively, whereas cAMP formation was reduced in atherosclerotic aortas to 7 (basal) and 96 (NaF) pmol cAMP.mg-1.min-1. The stimulatory effect of NaF (approximately 14-fold) remained unchanged. Since adenylyl and guanylyl cyclase have important functions in regulating vascular tone, reduced activities of both enzymes may contribute to the diminished relaxant and/or enhanced vasoconstricting effects of vasoactive compounds in atherosclerotic blood vessels.
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PMID:Hypercholesterolemia is associated with a reduced response of smooth muscle guanylyl cyclase to nitrovasodilators. 810 69

Effects of nitric oxide (NO)-containing compounds on opossum esophageal longitudinal smooth muscle in vitro were examined. Sodium nitroprusside (SNP) and authentic NO produced a biphasic concentration-dependent relaxation-contraction sequence in the esophageal longitudinal muscle (ELM) but only a concentration-dependent relaxation of the lower esophageal sphincter (LES) and no effect in the esophageal circular muscle. A cell membrane-permeable analogue of guanosine 3',5'-cyclic monophosphate (cGMP), 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) also produced relaxation-contraction sequence in the ELM and relaxation of the LES. The guanylate cyclase inhibitors methylene blue (MB) and LY-83583 increased resting tone and had no significant effect on SNP-induced relaxation of ELM. However, they abolished the SNP- and NO-induced contraction of ELM. The cyclooxygenase inhibitor indomethacin had no effect on ELM relaxation and abolished the contractions due to SNP, NO, and 8-BrcGMP. These studies show that in the ELM 1) SNP, authentic NO, and 8-BrcGMP cause a biphasic relaxation-contraction sequence; 2) MB and LY-83583 blocked contraction but not the relaxation associated with SNP and NO; and 3) indomethacin blocked contractions but not the relaxation due to SNP, NO, and 8-BrcGMP. These results suggest that in the ELM, NO donors exert an inhibitory action that is largely cGMP independent and an excitatory action via a cGMP-dependent pathway involving endogenous eicosanoids of the cyclooxygenase pathway.
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PMID:Biphasic effect of SNP on opossum esophageal longitudinal muscle: involvement of cGMP and eicosanoids. 810 38

We have analyzed the role of nitric oxide (NO), an unorthodox and novel neuromodulator, on luteinizing hormone-releasing hormone (LHRH) secretion. Sodium nitroprusside (SNP), an NO donor, was used to challenge LHRH neurons using both hypothalamic explants and an immortalized neuronal cell line (GT1 cells) in vitro. In both paradigms, SNP was able to stimulate LHRH release in a dose-dependent manner. This action of SNP was accompanied by an elevation in both extra- and intra-cellular cGMP levels. In addition, exposure of LHRH cells (GT1-7 cells) to increasing concentrations of a soluble analog of cGMP (8-Br-cGMP) enhanced LHRH release in a dose-dependent manner, indicating that LHRH neurons have the intrinsic ability to respond to the intracellular messenger elicited by NO, i.e., cGMP. Furthermore, sodium nitroprusside-induced LHRH secretion from GT1-7 cells was blocked, in a dose-dependent manner, by Rp-8-Br-cGMPS, a cGMP analog which blocks cGMP-dependent protein kinase. These data clearly demonstrate that NO stimulates LHRH secretion by activating guanylate cyclase, and support a potential role of NO as a neuroactive agent involved in the control of LHRH secretion and, thereby, reproductive functions.
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PMID:Nitric oxide regulates luteinizing hormone-releasing hormone secretion. 810 81

To elucidate the sequence of events between the release of neurotransmitters and cavernous smooth muscle relaxation in erection, we studied the role of the cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) systems. In a well-established simian model, the effects of specific agonists and antagonists of the intracellular sequence for smooth muscle relaxation and potassium channel openers on the intracavernous pressure were examined. Sodium nitroprusside (10(-3) M), a nitric oxide releaser and thus a stimulant of the cGMP system, caused an increase in the intracavernous pressure from 82 to 115 cm H2O for 7 to 19 min and penile diameter from 24.8 +/- 2.28 to 43 +/- 4.87 mm. When nitroprusside was injected after methylene blue (10(-3) M), a specific antagonist of the enzyme guanylate cyclase, intracavernous pressure rise decreased significantly, but cromakalin, a potassium channel opener, provoked excellent increases after the block. A smaller dose of sodium nitroprusside (10(-4) M) caused an increase in intracavernous pressure from 35 to 85 cm H2O for 7 to 11.5 min. When nitroprusside was injected after zaprinast, a phosphodiesterase inhibitor, the increase in pressure ranged from 80 to 116 cm H2O for 15 to 30 min. Prostaglandin E1, an activator of the cAMP system, caused an increase in the intracavernous pressure of 20-80 cm H2O for 5 to 10 min, and an increase in penile diameter from 25 +/- 2.22 to 35 +/- 3.48 mm. The erectile response to PGE1, but not to cromakalin, was nearly abolished by ethylmaleimide, an adenylate cyclase blocker. The response to nitroprusside was significantly greater (P < 0.05) than to PGE1. Both systems, cAMP and cGMP, may be involved in cavernous smooth muscle relaxation, and cGMP is probably the predominant intracellular second messenger in penile erection in monkeys. Stimulants of the cGMP system, such as nitric oxide releasers, could represent a more physiological and effective approach in the treatment of erectile dysfunction.
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PMID:Intracellular mechanism of penile erection in monkeys. 815 77

Cells isolated from the trabecular meshwork (TM) of a male glaucoma patient were transformed by transfection with an origin defective mutant of SV40 virus. Transformation dramatically increased the growth rate of these cells (designated HTM-3 cells), allowing biochemical and pharmacological characterization. The HTM-3 cells had cytoskeletal components that were reported to be present in TM tissue and non-transformed TM cells. Vimentin, tubulin and smooth muscle specific alpha-actin, but not desmin, were localized in these cells by immunocytochemistry. The extracellular matrix components collagen types I, III and IV, fibronectin and laminin were found in HTM-3 cells as well as their non-transformed parental cells. As predicted, the protein profile of the HTM-3 cells revealed by two-dimensional gel electrophoresis was different from that of the non-transformed cells, probably due to the enhanced growth characteristics of these cells. Furthermore, HTM-3 cells had various intracellular second messenger systems that responded to pharmacological agents. Forskolin, prostaglandin E2, beta-adrenergic and adenosine A2 agonists stimulated the adenylyl cyclase in these cells, whereas muscarinic, serotonergic, dopaminergic and other agonists were ineffective. Sodium nitroprusside increased the intracellular concentration of cGMP, demonstrating the presence of a functional guanylyl cyclase. Phospholipase C activity in these cells was also detected. Muscarinic agonists, histamine and bradykinin, but not adrenergic, serotonergic agonists or prostaglandins, increased phosphoinositide turnover. These drug responses of HTM-3 cells agree with published data on primary TM cells and TM tissues, suggesting that the transformed cells may be a valid substitute for certain pharmacological studies of TM.
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PMID:Preliminary characterization of a transformed cell strain derived from human trabecular meshwork. 815 26

Nitric oxide synthase(NOS) inhibitor,N omega-nitro-L-arginine methyl ester (L-NAME, 10-300 mg/kg) and L-NG-monomethyl-arginine (L-NMMA, 30-300 mg/kg) suppressed the swellings of adjuvant-injected paw of rats (25-54%) at day 2 and 8 when dosed intraperitoneally and orally for 4 days from day -1 to day 2 after adjuvant. L-NAME (30-300 mg/kg) also suppressed the edema of the non adjuvant-injected paws (15-42%) at day 28. Local injection of this inhibitor (2 and 10 mg/kg) was without effect. L-arginine (1 g/kg, i.p.), impaired the suppression by L-NAME. Bovine blood Cu, Zn-superoxide dismutase (SOD, 3 mg/kg, i.p.: 28% suppression) and L-NAME (30 mg/kg i.p.: 36% suppression) showed additive effect (52%) in adjuvant-injected paws at day 8 when co-injected. As the effect of 30 mg/kg L-NAME corresponded nearly to that of 10 mg/kg VoltarenR, this NOS inhibitor would be worth considering as an anti-inflammatory agent. Sodium nitroprusside (NO-donor) and methylene blue (guanylate cyclase inhibitor) had no effect. L-NAME was also suppressive when dosed after adjuvant inoculation and NO is involved in the development and maintenance of swelling.
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PMID:Nitric oxide and superoxide radical are involved in both initiation and development of adjuvant arthritis in rats. 816 99

Effects of sodium nitroprusside, 8-bromo cGMP and methylene blue on the glibenclamide-sensitive K+ current evoked by K+ channel openers in Xenopus oocytes were studied. Sodium nitroprusside (0.1-1 mM, an activator of guanylate cyclase) enhanced by 20-50% the K+ currents induced by KRN2391, nicorandil and cromakalim (K+ channel openers). 8-Bromo cGMP (1 mM) also increased the K+ current by 40-60%. Methylene blue (10 microM, an inhibitor of guanylate cyclase) irreversibly blocked the K+ current by about 20-30%. These results suggest that the activation of glibenclamide-sensitive K+ channels by K+ channel openers is modulated either positively or negatively by intracellular cGMP in oocytes.
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PMID:Modification by cGMP of glibenclamide-sensitive K+ currents in Xenopus oocytes. 838 23


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