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)

Evidence for the presence of multiple cyclic GMP (cGMP) systems in the vertebrate retina is examined. Levels of this cyclic nucleotide are characteristically high in the photoreceptor cell, whereas in the inner retina they are similar to those found in other areas of the central nervous system. Guanylate cyclase and cGMP phosphodiesterase show a similar uneven distribution, with very high levels of activity in outer segments. At least three forms of guanylate cyclase, one of which may be unique to the photoreceptor cell, have been described. Similarly, differences in the regulation of cGMP phosphodiesterase within localized areas of retina indicate the existence of multiple forms of this enzyme. Factors that influence cGMP levels also have regionally variable effects. Light adaptation leads to reduced cGMP levels in the distal retina, whereas inner retina layers do not show parallel changes. Calcium suppresses the formation of cGMP in photoreceptors, but has no effect or stimulates cGMP formation in the inner retina. Cellular depolarization appears to reduce levels of cGMP in photoreceptors and increases it in the inner retina. Furthermore, endogenous proteins whose phosphorylation is apparently controlled by cGMP seem to be localized to specific retinal cells or subcellular organelles. These data lead to the conclusion that multiple cGMP systems exist in the retina, each with a distinct location and function.
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PMID:Cyclic GMP systems in the retina. 613 83

Changes have been revealed in the function of cyclic GMP system of thymus and liver of irradiated (8 Gy) mice. In the thymus the cGMP level increased during the first 60 min following irradiation. In the liver the concentration of cGMP exhibited two peaks: 30 min and 24 hr after irradiation. The changes observed in the cGMP level are connected with the increased guanylate cyclase activity of thymocytes and liver of irradiated mice and, less likely, with changes in the activity of cGMP phosphodiesterase of these tissues.
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PMID:[Postirradiation changes in the cGMP system of the mouse thymus and liver]. 613 42

Cyclic guanosine 3'5'-monophosphate was isolated and purified from Mycobacterium smegmatis TMC 1515 using ion exchange chromatography. It was characterized by thin layer chromatography and radioimmunoassay. Guanylate cyclase and cGMP phosphodiesterase were detected in the cytosolic and particulate (37,000 X g pellet) fractions respectively. On the basis of our observations, cGMP appears to play a dual role (i) at the time of induction of cell proliferation and (ii) protects the bacteria against unfavourable surroundings during stationary phase of the growth. This is the first report demonstrating presence of cGMP, guanylate cyclase and cGMP phosphodiesterase in mycobacteria.
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PMID:Characterization and metabolism of cyclic guanosine 3'5'-monophosphate in Mycobacterium smegmatis. 614 17

A 26 amino acid synthetic peptide fragment of atrial natriuretic factor (ANF) relaxed isolated rabbit aortic segments in which the endothelium was either intact or functionally destroyed. The relaxations were temporally associated with increases in levels of cGMP with no change in the levels of cAMP. The ANF-induced increases in cGMP were also observed in aortic segments pretreated with calcium-free buffer or the cGMP phosphodiesterase inhibitor M&B 22,948. Qualitatively similar results were obtained for sodium nitroprusside. ANF selectively activated particulate guanylate cyclase, having no effect on the soluble form of the enzyme. Thus, the direct (endothelium-independent) vasodilator effect of ANF may be mediated via increased tissue levels of cGMP. ANF appears to increase vascular cGMP levels by activation of particulate guanylate cyclase.
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PMID:Atrial natriuretic factor elicits an endothelium-independent relaxation and activates particulate guanylate cyclase in vascular smooth muscle. 615 Apr 86

Changes in the functioning of the cGMP system of the thymocytes and liver of mice subjected to 8 Gy roentgen irradiation were found. Within one hour after irradiation an increase in the cGMP level in thymocytes was noted; two rises in the cGMP concentration in the liver were established, at 0.5 and 24 hours after irradiation. These changes in the cGMP level were correlated to an increase in the guanylate cyclase activities in the thymocytes and liver of the mice subjected to irradiation, and to a lesser extent to changes in the activities of cGMP phosphodiesterase in these tissues. A post-irradiation increase in the rat liver guanylate cyclase activity was also observed. A decrease in cGMP phosphodiesterase activity in the liver of the irradiated mice was followed by a change in the enzymatic kinetics and an increase in cGMP phosphodiesterase thermolability. The post-irradiation rise in guanylate cyclase activity was produced by activation of the enzyme.
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PMID:The cGMP system in irradiated animals. Changes in cGMP content and activities of guanylate cyclase and cyclic nucleotide phosphodiesterase. 615 Jun 3

The responses of the bovine retractor penis muscle to field stimulation of intramural nerves in vitro was investigated using micro-electrode and extracellular (sucrose gap) techniques. In the absence of tone single pulses or trains of stimuli (1-50 Hz 0.1-0.5 m.sec) produced e.j.p.s and a decrease in membrane resistance; spike potentials were not observed. E.j.p.s often small in amplitude (3-5 mV to single pulse) and accompanied by contractions in almost all preparations were noradrenergic, abolished by guanethidine (1-3 x 10(-5) M) and tetrodotoxin (3.5 x 10(-6) M) but not by prazosin (0.05 - 1.4 x 10(-6) M). Prazosin abolished the depolarization and contraction produced by added NA (0.02 - 2 x 10(-8) moles). TEA (10(-2) M) depolarized the membrane and initiated spontaneous activity; e.j.p.s and contractions were enhanced and prolonged but no spikes were observed. Atropine (0.5 x 10(-6) M) increased and physostigimine (1-5 x 10(-6) M) decreased e.j.p.s and contractions indicating a cholinergic regulatory component in the release of the excitatory transmitter. In the presence of tone, nerve stimulation produced i.j.p.s. and relaxations which were unaffected by apamin (5 x 10(-7) M), atropine (3 x 10(-6) M), guanethidine (3 x 10(-5) M), phentolamine (5 x 10(-6) M) and propranolol (4 x 10(-6) M) but were abolished by tetrodotoxin (3.5 x 10(-7) M) suggesting their mediation by non-adrenergic non-cholinergic (NANC) nerves. Sodium nitroprusside (10(-10) - 10(-8) moles), which increases cyclic GMP, also hyperpolarized the membrane and relaxed the BRP. Those responses and those to inhibitory nerve stimulation were antagonized by oxyhaemoglobin which inhibits guanylate cyclase. 2-O-propoxyphenyl-8-azapurin-6-one (M & B 22948 3-9 x 10(-6) M) which inhibits cGMP-specific phosphodiesterase, enhanced the relaxation but not the i.j.p. TEA (10(-2) M) initially depolarized the membrane potential and raised tone. In the sucrose gap inhibitory potentials were abolished; the mechanical relaxation was not and a small contractile component emerged. Electrical and mechanical inhibitory components in the bovine retractor penis may not be correlated.
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PMID:Electrical and mechanical responses of the bovine retractor penis to nerve stimulation and to drugs. 615 68

Since nicorandil (SG-75) is a potent vasodilator, has a terminal NO2 group, resembles nitroglycerin in its hemodynamic actions, which are likely to be mediated by cyclic GMP (cGMP), whether or not nicorandil relaxes vascular smooth muscle by a similar mechanism was investigated in isolated circular strips of bovine coronary arteries. It was found that nicorandil at concentrations producing dose-dependent relaxation up to 94% (0.47-473 microM) similar raised cGMP levels in the strips up to 10-fold of the control value, and that this effect preceded the mechanical response. When the breakdown of cGMP was blocked by a predominant inhibitor of cGMP phosphodiesterase, 2-o-propoxyphenyl-8-azapurin-6-one, both actions of nicorandil (cGMP increase and relaxation) were significantly potentiated. Inhibition of cGMP formation by methylene blue and, to a lesser extent, by ferricyanide, which antagonize guanylate cyclase activation by NO-yielding substances, significantly attenuated both actions of nicorandil under study. It was further demonstrated that nicorandil as well as nitroglycerin was a potent stimulator of soluble guanylate cyclase activity from bovine coronary arteries in vitro, an effect that was also susceptible to blockade by methylene blue or ferricyanide. These results indicate that nicorandil relaxes vascular smooth muscle, at least in part, through cGMP.
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PMID:Cyclic GMP as possible mediator of coronary arterial relaxation by nicorandil (SG-75). 619 Nov 33

Calmodulin has been isolated from the outer segment of toad (Bufo marinus) photoreceptors. Bioelectric processes have been recorded from the same preparation during various experimental conditions. The results led to the conclusion that during illumination the rotation of the chemoreceptors opens the Ca channels, and free Ca is versed into the intermembrane space of the outer segment. Changes of this free Ca concentrations depend on fast influx and slower removal (mainly dependent on Ca binding on calmodulin and back-diffusion into the disc membrane). The changes of the free Ca concentrations generate the changing hyperpolarization, a Ca-dependent process of first phases of encoding the photic stimulus. The effectiveness of Ca to generate the oscillating hyperpolarization depends on optimum state of bioelectric potentials. This potential seems to be regulated by the effective decrease of cGMP concentrations by the increased activity of the cGMP phosphodiesterase during illumination (a sudden and gross regulation). A finer regulation is exerted by Ca during its release and removal (e.g., Ca-dependent decrease of Na channels, decreased release of cGMP by Ca-dependent inhibition of guanylate cyclase activity and increased phosphodiesterase activity by both free Ca and Ca-bound calmodulin).
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PMID:Illumination dependent hyperpolarization of the photoreceptor outer segment membrane (role of calcium, cyclic GMP and calmodulin). 627 52

YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole] inhibited the aggregation of and ATP release from washed rabbit platelets induced by arachidonic acid (AA), collagen, U46619, platelet-activating factor (PAF), and thrombin in a concentration-dependent manner. YC-1 also disaggregated the clumped platelets caused by these inducers. The thromboxane B2 formation caused by collagen, PAF, and thrombin was inhibited by concentrations of YC-1 that did not affect formation of thromboxane B2 and prostaglandin D2 caused by AA. YC-1 suppressed the increase of intracellular Ca2+ concentration and generation of inositol 1,4,5-trisphosphate caused by these five aggregation inducers. Both the cAMP and cGMP contents of platelets were increased by YC-1 in a concentration- and time-dependent manner. Like sodium nitroprusside, YC-1 potentiated formation of cAMP caused by prostaglandin E1 but not that by 3-isobutyl-1-methylxanthine. Adenylate cyclase and cAMP phosphodiesterase activities were not altered by YC-1. Activity of cGMP phosphodiesterase was unaffected by YC-1. Activities of guanylate cyclase in platelet homogenate and cytosolic fraction were activated by YC-1, whereas particulate guanylate cyclase activity was unaffected. The antiplatelet effect of sodium nitroprusside but not that of YC-1 was blocked by hemoglobin and potentiated by superoxide dismutase. After intraperitoneal administration for 30 minutes, YC-1 prolonged the tail bleeding time of conscious mice. These data indicate that YC-1 is a direct soluble guanylate cyclase activator in rabbit platelets. It may also possess antithrombotic potential in vivo.
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PMID:YC-1, a novel activator of platelet guanylate cyclase. 752 71

Atrial natriuretic factor (ANF) reduces the volume of atrial myocytes by inhibiting Na+/K+/2Cl- cotransport. We determined the role of cGMP and cAMP in ANF-induced shrinkage by using digital video microscopy to measure cell volume; volumes are reported relative to control. ANF (1 mumol/L) reversibly reduced atrial cell volume from 1.0 to 0.915 +/- 0.005 (mean +/- SEM). This effect was mimicked by 10 mumol/L 8-bromo-cGMP (8-Br-cGMP), which decreased myocyte volume to 0.894 +/- 0.007 with an ED50 of 0.99 +/- 0.05 mumol/L. In contrast, 100 mumol/L 8-bromo-cAMP (8-Br-cAMP) did not affect volume, and activating the cAMP pathway with 100 mumol/L 8-Br-cAMP did not alter the volume decrease caused by 8-Br-cGMP or ANF. Inhibition of Na+/K+/2Cl- cotransport with bumetanide (1 mumol/L) also reduced cell volume and prevented further shrinkage on subsequent exposure to 8-Br-cGMP. Similarly, 8-Br-cGMP (10 mumol/L) prevented further shrinkage by ANF. Block of Na(+)-H+ exchange, a participant in volume regulation in other cells, did not alter the response to 8-Br-cGMP. More evidence implicating cGMP was obtained by altering its metabolism. LY83583 (10 mumol/L), a guanylate cyclase inhibitor, blocked ANF-induced cell shrinkage. Zaprinast (100 mumol/L), a cGMP-specific phosphodiesterase inhibitor, markedly potentiated the effect of a threshold concentration of ANF (0.01 mumol/L). The actions of ANF, LY83583, and zaprinast on cGMP levels were verified by radioimmunoassay. These data strongly support the idea that the cGMP cascade is the intracellular signaling pathway responsible for ANF-induced atrial cell shrinkage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:cGMP and atrial natriuretic factor regulate cell volume of rabbit atrial myocytes. 755 21


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