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)

We studied the localizations of alpha 1 and beta 1 subunits of soluble guanylate cyclase using in situ hybridization. The beta subunit was widely distributed in most neurons throughout the brain, with different levels of expression. The alpha 1 subunit was also distributed throughout the brain; however, it was located in more limited regions. Both subunits were expressed markedly in the glomerular layer of the olfactory bulb, dorsal and ventral striatum, and several regions in the brainstem. Regions with little or no alpha 1 subunit expression, but with marked expression of the beta 1 subunit included the olfactory bulb except for the glomerular layer, pyramidal cell layer in CA1 and granular cell layer in the dentate gyrus of the hippocampus, and many brainstem nuclei. The above regions expressing both subunits are suggested to contain active soluble guanylate cyclase as a target for nitric oxide, and thus may be involved in cellular signal transduction.
Brain Res Mol Brain Res 1993 Dec
PMID:Localizations of alpha 1 and beta 1 subunits of soluble guanylate cyclase in the rat brain. 790 52

In Dictyostelium discoideum extracellular cyclic AMP (cAMP), as shown by previous studies, induces a transient accumulation of intracellular cyclic guanosine-5'-monophosphate (cGMP), which peaks at 10 s and recovers basal levels at 30 s after stimulation, even with persistent cAMP stimulation. Additional investigations have shown that the cAMP-mediated cGMP response is built up from surface cAMP receptor-mediated activation of guanylyl cyclase and hydrolysis of cGMP by phosphodiesterase. The regulation of these activities was measured in detail on a seconds time-scale, demonstrating complex adaptation of the receptor, allosteric activation of cGMP-phosphodiesterase by cGMP, and potent inhibition of guanylyl cyclase by Ca2+. In this paper we present a computer model that combines all experimental data on the cGMP response. The model is used to investigate the contribution of each structural and regulatory component in the final cGMP response. Four models for the activation and adaptation of the receptor are compared with experimental observations. Only one model describes the magnitude and kinetics of the response accurately. The effect of Ca2+ on the cGMP response is simulated by changing the Ca2+ concentrations outside the cell (Ca2+ influx) and in stores (IP3-mediated release) and changing phospholipase C activity. The simulations show that Ca2+ mainly determines the magnitude of the cGMP accumulation; simulations are in good agreement with experiments on the effect of Ca2+ in electropermeabilized cells. Finally, when cGMP-phosphodiesterase activity is deleted from the model, the simulated cGMP response is elevated and prolonged, which is in close agreement with the experimental observations in mutant stmF that lacks this enzyme activity. We conclude that the computer model provides a good description of the observed response, suggesting that the main structural and regulatory components have been identified.
Mol Biol Cell 1994 May
PMID:A model for cAMP-mediated cGMP response in Dictyostelium discoideum. 791 38

1. Guanylate cyclase plays an important role in the visual cycle. Here we report the mRNA expression for the atrial natriuretic peptide receptor type A form of guanylate cyclase (ANPRA) in human retina. 2. Polymerase chain reaction using two sets of primers on the cDNAs reverse-transcribed from human retinal poly(A)+ RNA amplified two products under two different reaction conditions. The primers used in the reaction were designed from the reported sequence of human placental ANPRA cDNA. 3. Sequencing of the amplified products showed 100% sequence homology to the human placental ANPRA gene. Northern blot analysis indicated the presence of a 4.4-kb ANPRA mRNA in human retina, similar to that present in human brain.
Cell Mol Neurobiol 1994 Feb
PMID:Expression of mRNA for atrial natriuretic peptide receptor guanylate cyclase (ANPRA) in human retina. 795 58

2-Methyl-2-nitrosopropane (MNP) has long been known to undergo photochemical and thermal decomposition, generating di-tert-butyl nitroxide, in organic solvent. The present study was undertaken to demonstrate that MNP can be used as a caged-nitric oxide (NO), which can liberate NO upon illumination. Photolysis of MNP leads to the generation of tert-butyl radical and NO, as detected by spin-trapping/ESR spectroscopy and by oxyhemoglobin/visible spectroscopy, respectively. Using soluble guanylate cyclase in neuroblastoma N1E-115 cells as an NO target, we found that MNP in the presence of light caused a dose- and time-dependent increase in cGMP. Finally, illumination of a solution of MNP was also found to induce relaxation of preconstricted isolated rat pulmonary artery rings. These studies demonstrated that MNP can be useful biochemical research tool for delivering NO in a controlled manner, by using light.
Mol Pharmacol 1994 Oct
PMID:Biological studies of a nitroso compound that releases nitric oxide upon illumination. 796 50

Diazetidine-di-N-oxide derivatives have been found capable of the nonenzymatic generation of nitric oxide by a principally new mechanism of nitric oxide splitting at physiological pH values. The effect of the synthesized compounds on human platelet soluble guanylate cyclase activity and ADP-induced human platelets aggregation were studied. Four of 7 derivatives studied exhibited a distinct correlation between the intensity of platelet guanylate cyclase activation, inhibition of platelets aggregation and acceleration of their disaggregation. The NO-dependent mechanism of guanylate cyclase activation and intraplatelet cGMP accumulation are suggested to be responsible for antiaggregatory/disaggregatory properties of the compounds used. Data presented allow us to regard 1,2-diazetidine-di-N-oxide derivatives as antiaggregatory agents of a new class.
Biochem Mol Biol Int 1994 Aug
PMID:Inhibition of ADP-induced human platelet aggregation by a new class of soluble guanylate cyclase activators capable of nitric oxide generation. 798 64

The role of intracellular signal transduction mechanisms in regulating the motility and metabolism of rat spermatozoa in undiluted caudal epididymal fluid (CEF) was examined. Samples of CEF containing immotile spermatozoa were exposed to drugs and other agents that either stimulate signal transduction pathways or mimic the action of their second messengers. Under these conditions, sperm motility in 25-30 nl of CEF was stimulated by calcium ions (Ca2+), N2,2'-O-dibutyrylguanosine 3':5'-cyclic monophosphate (dibutyryl cGMP), cyclic adenosine 3':5'-monophosphate (cAMP), N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (dibutyryl cAMP), 8-bromoadenosine 3':5'-cyclic monophosphate (8-bromo cAMP), caffeine, theophylline and bicarbonate ions (HCO3-). Other agents such as magnesium ions (Mg2+), veratridine, phospholipase C (PLC), ionophore A23187, 1,2-dioctenoyl-sn-glycerol (DAG), phorbol 12-myristate 13-acetate, phospholipase A2 (PLA2), arachidonic acid, and melittin did not significantly influence motility. In the presence of radiolabelled energy substrates, untreated (immotile) spermatozoa in samples of CEF utilised D-[U-14C]glucose and [1-14C]acetate as exogenous energy sources for oxidative metabolism. No detectable 14C-lactate was produced, and none of the drugs altered the rate of glycolytic or oxidative metabolism. The findings suggest that the motility of rat caudal epididymal spermatozoa is regulated by Ca2+ and the guanylate cyclase and adenylate cyclase pathways, but not through the PLC and PLA2 pathways. Also, their metabolism of exogenous substrate was uncoupled from the induction of motility, and their oxidative capacity exceeded the rate of flux of glucose-carbon through the glycolytic pathway.
Mol Reprod Dev 1994 May
PMID:Intracellular signal transduction mechanisms of rat epididymal spermatozoa and their relationship to motility and metabolism. 804 68

The endothelial cell has a unique intrinsic feature: it produces a most potent vasopressor peptide hormone, endothelin (ET-1), yet it also contains a signaling system of an equally potent hypotensive hormone, atrial natriuretic factor (ANF). This raises two related curious questions: does the endothelial cell also contain an ET-1 signaling system? If yes, how do the two systems interact with each other? The present investigation was undertaken to determine such a possibility. Bovine pulmonary artery endothelial (BPAE) cells were chosen as a model system. Identity of the ANF receptor guanylate cyclase was probed with a specific polyclonal antibody to the 180 kDa membrane guanylate cyclase (mGC) ANF receptor. A Western-blot analysis of GTP-affinity-purified endothelial cell membrane proteins recognized a 180 kDa band; the same antibody inhibited the ANF-stimulated guanylate cyclase activity; the ANF-dependent rise of cyclic GMP in the intact cells was dose-dependent. By affinity cross-linking technique, a predominant 55 kDa membrane protein band was specifically labeled with [125I]ET-1. ET-1 treatment of the cells showed a migration of the protein kinase C (PKC) activity from cytosol to the plasma membrane; ET-1 inhibited the ANF-dependent production of cyclic GMP in a dose-dependent fashion with an EC50 of 100 nM. This inhibitory effect was duplicated by phorbol 12-myristate 13-acetate (PMA), a known PKC-activator. The EC50 of PMA was 5 nM. A PKC inhibitor, 1-(5-isoquinolinyl-sulfonyl)-2-methyl piperazine (H-7), blocked the PMA-dependent attenuation of ANF-dependent cyclic GMP formation. These results demonstrate that the 180 kDa mGC-coupled ANF and ET-1 signaling systems coexist in endothelial cells and that the ET-1 signal negates the ANF-dependent guanylate cyclase activity and cyclic GMP formation. Furthermore, these results support the paracrine and/or autocrine role of ET-1.
Mol Cell Biochem 1993 Mar 10
PMID:Interaction of atrial natriuretic factor and endothelin-1 signals through receptor guanylate cyclase in pulmonary artery endothelial cells. 809 23

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.
J Mol Endocrinol 1993 Apr
PMID:Nitric oxide stimulates cyclic GMP in human thyrocytes. 809 15

The heat stable enterotoxins (ST) of enterotoxigenic Escherichia coli (ETEC) cause diarrhoea by binding specific intestinal receptors. Precise histochemical localization of ST receptors could provide more information about the pathophysiology of secretory diarrhoea and the role of ST receptors in normal biology. To accomplish this, we quantitatively coupled biotin to the N-terminus of ST1b using biotin-X-X-N-hydroxysuccinimide ester. The derivatized toxin (BST) has an apparent Kd of 11.7 +/- 10 nM for rat brush border receptors. We used BST in an affinity panning cell-capture system, to validate its ability to discriminate between receptor-positive and receptor-negative cells. Cell lines expressing ST receptors (human colon carcinoma T84, and COS cells transfected with guanylyl cyclase-C (GC-C) ST receptor cDNA) were captured to streptavidin and anti-biotin-coated plates with high efficiency and specificity. This system provides a novel approach to screening cells for the presence of unique ST-binding proteins. BST was then used with streptavidin-gold to demonstrate the cellular topography of ST receptors at the light microscopic level. Villus enterocytes were intensely stained, but only a faint signal was observed in upper crypts of rat small intestine. Thus, a gradient of increasing receptor density was seen as upper crypt cells matured into villus enterocytes. Higher magnification revealed that ST receptors are concentrated at the apical aspect of villus enterocytes. Recently, guanylin, a putative endogenous ligand for ST receptors, has been localized to Paneth cells, at the base of intestinal crypts. Thus, ST receptors are concentrated in villus enterocytes, while guanylin appears to be produced at the base of the crypts.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Microbiol 1993 May
PMID:Ligand-based histochemical localization and capture of cells expressing heat-stable enterotoxin receptors. 810 72

Derivatives of diazetidine-di-N-oxides have been found capable of the nonenzymatic generation of nitric oxide by the principally new mechanism of the nitric oxide splitting at physiological pH values. The effect of the synthesized compounds on human platelet soluble guanylate cyclase activity as well as their spasmolytic and hypotensive action were studied. Four of 7 derivatives studied exhibited a distinct correlation between the ability of being decomposed with the nitric oxide formation, activation of soluble guanylate cyclase, and spasmolytic and antihypertensive activities. Among them, 3-brom, 4-methyl-3,4-tetramethylene-diazetidine-di-N-oxide has proved to be most effective, its spasmolytic effect being commensurable with glyceryl trinittrate activity. The revealed correlation allows us to regard 1,2-diazetidine-1,2-di-N-oxide derivatives as vasodilatory agents of a new class.
Biochem Mol Biol Int 1993 Jun
PMID:Derivatives of 1,2-diazetidine-1,2-di-N-oxides--a new class of soluble guanylate cyclase activators with vasodilatory properties. 810 89


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