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)

It has been shown that the content of cAMP in the rat thymus, spleen, and liver 1 and 3 days after gamma-radiation with 7.5 Gy decreases, and that of cGMP increases. Analogous dynamics has been revealed when studying adenylate cyclase and guanylate cyclase activities. The activity of cAMP and cGMP phosphodiesterases increased during the first period of study but subsequently it showed no distinction from the initial data level. The revealed postradiation changes in the content of cyclic nucleotides seem to be basically caused by the cyclases activity alterations.
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PMID:[Changes in the system of cyclic nucleotides in irradiated body tissues]. 289 67

A single class of saturable, specific binding sites for the circulating form of atrial natriuretic peptides, ANP(99-126), was identified in rat thymus and spleen and in isolated thymocytes and spleen cells using quantitative autoradiographic techniques. In the thymus, the relative potency of ANP analogs to inhibit [125I] ANP(99-126) binding was ANP(99-126) = ANP(103-126) greater than ANP(111-126) greater than ANP(103-125). ANP(103-123) could not displace [125I]ANP(99-126) binding. Addition of ANP(99-126) stimulated the formation of cyclic GMP in isolated thymocytes and spleen cells in a dose-dependent manner. Our results indicate that immune cells have specific ANP receptors which could be coupled to guanylate cyclase activation and may play a role in the regulation of the immune response.
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PMID:Atrial natriuretic peptide, ANP(99-126), receptors in rat thymocytes and spleen cells. 303 40

The levels of cyclic adenosine 3'5'-monophosphate (cAMP) in unstimulated (resting) peripheral blood thymus-derived lymphocytes (T cells) from normal old humans and young-adult Down's syndrome (DS) patients were markedly decreased when compared with those of young normal humans. By contrast, the cyclic guanosine 3'5'-monophosphate (cGMP) in resting T cells from normal old and young-adult DS patients were greatly increased. The cAMP/cGMP ratios for unstimulated T cells therefore declined in normal aged and DS subjects. The specific activity of adenylate cyclase (ATP pyrophosphate-lyase[cycling]E.C.4.6.1.1) was elevated in T cells from the aged and DS groups, whereas that of guanylate cyclase (GTP pyrophosphate-lyase[cycling]E.C.4.6.1.2) decreased with age and in DS. These results denote the existence of substantial age-related biochemical changes in peripheral T cells. An imbalance in resting cyclic nucleotide levels and their generating enzymes in T cells of normal aging and DS subjects might contribute to the immune dysfunction occurring both with aging and in DS.
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PMID:Alterations in cyclic nucleotides and cyclase-specific activities in T lymphocytes of aging normal humans and patients with Down's syndrome. 610 29

The subcellular repartition and the distinctive properties of guanylate cyclase (EC 4.6.1.2) vary according to the lymphocyte population studied and according to the presence of detergent. Guanylate cyclase of non-adherent peripheral lymphocytes and of thymus lymphocytes is recovered by more than 90% in the soluble fraction of the homogenate. Kinetics according to the substrate (5'-GTP-Mn2+) is Michaelian, the Ca2+ ion acts as an activator, especially in the case of blood lymphocytes, and the detergent has no effect on the enzyme activity. On the other hand, the guanylate cyclase of tonsil lymphocytes reside in the particulate fraction. It has non-Michaelian kinetics for the substrate, a strong stimulating effect of detergent, and an inhibitory effect of Ca2+. A comparison of the enzymatic activities of unseparated and of non-adherent tonsil lymphocytes obtained from the same donor points to a correlation between their T and B properties: predominant soluble activity in the T population and particulate guanyl cyclase activity in the B subset.
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PMID:Guanylate cyclase activity of human lymphocytes from peripheral blood, thymus, and tonsils. A comparative study. 613 46

The existence of Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C), the effect of gastrin on phospholipid metabolism and guanylate cyclase activity were investigated to elucidate the cellular mechanism of action of gastrin on the corporal mucosa of the canine stomach. Protein kinase activity was determined by measuring the incorporation of [32P] into calf thymus H1-histone from [32P]-ATP. One unit of protein kinase was defined as the amount of enzyme which incorporated 1 pmol of phosphate from ATP into H1-histone. Protein kinase C was found in 100,000xg supernatant of homogenate fractionated by a DEAE-cellulose column chromatography. Characteristics of further purified protein kinase C, such as dependency on divalent cations and phospholipids, were in agreement with those of previously reported protein kinase C in other tissues. Furthermore, the gastric corporal mucosa was found to contain protein kinase C in large quantities. The specific activity of protein kinase C was 26,000 units/mg protein. The phospholipid metabolism was evaluated by the incorporation of [14C]-glycerol-3-phosphate and the change of the radioactivity of [32P] in individual phospholipids. Each phospholipid was extracted from the gastric corporal mucosa and isolated by thin layer chromatography. Guanylate cyclase activity was determined by measuring the cGMP produced, using radioimmunoassay. Gastrin significantly increased the incorporation of [14C]-glycerol-3-phosphate into phosphatidylethanolamine in the presence of acetylcholine (Ach). Ach increased the uptake of the tracer into phosphatidylinositol significantly, and the increase was enhanced by the simultaneous addition of gastrin. In the experiments with [32P]-labeled phospholipids, gastrin increased the incorporation of [32P] into phosphatidylethanolamine significantly. The significant increase of the radioactivity in phosphatidylinositol by Ach failed to be enhanced by gastrin, but that of phosphatidylethanolamine by Ach was enhanced by gastrin. No stimulation of guanylate cyclase activity by gastrin was detected in the dispersed gastric corporal mucosal cells. These results indicate that gastric corporal mucosa was one of the most abundant tissues in which protein kinase C was contained, when compared with various mammalian tissues previously reported by Minakuchi, Nishizuka, et al. Nishizuka et al, recently proposed the novel hypothesis that phosphatidylinositol turnover activated by cAMP-independent agonists will be essentially required to activate protein kinase C. Our results suggest that gastrin can provoke phospholipids turnover including phosphatidylinositol turnover in gastric corporal mucosa. Therefore, our data indicate the possibility that the protein kinase C system plays an important role in the cellular mechanism of action of gastrin on gastric corporal mucosa.
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PMID:[The cellular mechanism of action of gastrin on the corporal mucosa of the canine stomach. (2) Ca2+-activated, phospholipid-dependent protein kinase and phospholipid turnover--possible mediator of gastrin action]. 613 23

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

The role of cyclic nucleotides in the regulation of lymphocyte growth and differentiation remains controversial, as an adequate characterization of the key enzymes, adenylate cyclase and guanylate cyclase, in the plasma membrane of lymphocytes is still lacking. In this study, calf thymus lymphocytes were disrupted by nitrogen cavitation and various cellular fractions were isolated by differential centrifugation and subsequent sucrose density ultracentrifugation. As revealed by the chemical composition and the activities of some marker enzymes, the plasma membrane fraction proved to be highly purified. Nucleotide cyclases were present in the plasma membranes in high specific activities, basal activities of adenylate cyclase being 13.7 pmol/mg protein per min and 34.0 pmol/mg protein per min for the guanylate cyclase, respectively. Adenylate cyclase could be stimulated by various effectors added directly to the enzyme assay, including NaF, GTP, 5'-guanylyl imidodiphosphate, Mn2+ and molybdate. Addition of beta-adrenergic agonists only showed small stimulating effects on the enzyme activity in isolated plasma membranes. Basal activity of adenylate cyclase as well as activities stimulated by NaF or 5'-guanylyl imidodiphosphate exhibited regular Michaelis-Menten kinetics. Activation by both agents only marginally affected the Km values, but largely increased Vmax. The activity of the plasma membrane-bound guanylate cyclase was about 10-fold enhanced by the nonionic detergent Triton X-100 and high concentrations of lysophosphatidylcholine, but was slightly decreased upon addition of the alpha-cholinergic agonist carbachol. Basal guanylate cyclase indicated to be an allosteric enzyme, as analyzed by the Hill equation with an apparent Hill coefficient close to 2. In contrast, Triton X-100 solubilized enzyme showed regular substrate kinetics with increasing Vmax but unaffected Km values. Thus the lymphocyte plasma membrane contains both adenylate cyclase and guanylate cyclase at high specific activities, with properties characteristic for hormonally stimulated enzymes.
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PMID:Characterization and subcellular localization of nucleotide cyclases in calf thymus lymphocytes. 614 2

The effect of dibutyryl cyclic guanosine monophosphate (dbc-GMP) on butylated hydroxyanisole (BHA)-induced suppression of the primary in vitro thymus-dependent antibody response of BDF1 mouse spleen cultures was studied. When added at 0 hr relative to antigen addition, 1 mg of dbc-GMP (8 mM) restored by greater than 70% the BHA-inhibited primary immunoglobulin (Ig)M plaque-forming cell (PFC) response to sheep erythrocytes (SRBC). The suppression was not reversed by the addition of 50 microgram of dibutryl cyclic adenosine monophosphate (dbc-AMP), which is known to reverse suppressor T-cell activity. The addition of 10 mM extracellular calcium (Ca2+) at the same time as antigen to BHA-inhibited cultures resulted in more than 80% restoration of the anti-SRBC PFC response. Quantitation of c-GMP by radioimmunoassay demonstrated that BHA lowered by 58% the c-GMP content of splenic lymphocytes and abrogated the ability of lipopolysaccharide of E. coli (LPS) to elevate c-GMP levels in splenic lymphocytes. The data suggest that BHA exerts its immunosuppressive effect on the primary in vitro antibody response by inhibiting guanylate cyclase activity and effectively lowering c-GMP levels; exogenous dbc-GMP and Ca2+ can freely reverse the immunosuppressive effect of BHA.
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PMID:Restoration by cyclic guanosine monophosphate and extracellular calcium of butylated hydroxyanisole-suppressed primary murine thymus-dependent antibody response. 627 34

BM 12,531 (azimexon) is an experimental immunomodulating agent which augments cellular immune responses in vivo. This study indicates that BM 12,531, while not directly mitogenic for human peripheral blood lymphocytes nor guinea pig peritoneal macrophages, potentiates the proliferative effects of phytohemagglutinin and a lymphokine, respectively. The optimal effects (0.001--0.01 microgram/ml) are somewhat greater in magnitude than those of levamisole. Unlike levamisole, BM 12,531 has no effect on cyclic 3',5' GMP levels or on guanylate cyclase activity of lymphocytes. The data suggest that both the thymus-derived lymphocyte and the monocyte-derived macrophage are cell targets of BM 12,531 action at concentrations achievable in vivo.
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PMID:Effects of BM 12,531 (azimexon) on in vitro lymphocyte and macrophage proliferation. 723 28

The changes in cAMP and cGMP content in rat spleen and thymus lymphocytes after irradiation in doses of 0.5 and 1 Gy, are determined, indicating to significant disturbances in the system of cyclic nucleotides. Radiation affected the functioning of enzymes both of synthesis and hydrolysis of cAMP and cGMP in spleen lymphocytes. The activity of adenylate cyclase and guanylate cyclase did not change in thymocytes after the exposure, while the activity of phosphodiesterase of cyclic nucleotides slightly increased.
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PMID:[Post-radiation disturbances in the cyclic nucleotide system in rat spleen and thymus lymphocytes]. 858 57


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