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

---

Query: EC:4.6.1.2 (guanylate cyclase)
8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bacterial lipopolysaccharides (LPS) greatly increase cGMP levels in short term cultures of rat fetal liver cells without affecting the concentration of cAMP. This effect is produced by very small (1 ng) amounts of LPS and is both dose and time dependent. The time dependence is characterized by an initial lag period of 60-120 min followed by a rapid, persistent increase in cGMP levels. Since this time course suggests that synthesis of an intermediate might play an important role in the cGMP elevation, a series of experiments was done to evaluate the effect of LPS on DNA, RNA, and protein (macromolecular) synthesis. LPS did not measurably effect total macromolecular synthesis. However, inhibitors of RNA and protein synthesis markedly reduced cGMP levels in LPS-treated cells, whereas inhibition of DNA synthesis did not. Addition of sodium nitroprusside to control and inhibitor-treated cultures produced large equivalent increases of cGMP levels in both cases, indicating that the cells present were fully capable of responding to a stimulus of guanylate cyclase. Taken together, this data suggests that expression of the LPS-cGMP response in fetal liver cells is dependent on synthesis of an intermediary protein(s) during the lag phase.
...
PMID:Further characterization of the effect of bacterial lipopolysaccharide preparations on cyclic GMP levels: the importance of macromolecular synthesis. 241 34

Met-enkephalin (ME) exerts a bimodal effect on functional activities of rat peritoneal macrophages (PM); in a range of low concentration (10(-9)-10(-7)M) antibody dependent cellular cytotoxicity (ADCC) was markedly stimulated with a simultaneous decrease of Fc gamma receptor (Fc gamma R) medicated phagocytosis while the opposite was observed at 10(-6)-10(-5)M concentrations. Studying the possible underlying mechanism(s) the followings were recorded: (1) ME in all applied concentrations induced an early Na+ influx which was followed by a Ca2+ efflux in the range of low concentrations. In the range of high concentrations Na+ influx was accompanied by a Ca2+ influx. (2) ME at 10(-8) M concentration induced a rise in cGMP level with a plateau in the 60-120th min of incubation. This effect was prevented by 10(-5) M of naloxone. At 10(-6) M concentration a transient rise of cAMP level was recorded which was not affected by naloxone. (3) Verapamil in 10(-6) M abolished both the Ca2+ influx and the rise in cAMP level induced by 10(-6)-10(-5) M ME but not the rise in cGMP level induced by lower ME concentrations. (4) cAMP elevation by high ME concentrations was abolished by enkephalinase inhibitory puromycin. (5) PM-enkephalinase as assessed by the cleavage of fluorogenic substrate L-alanine beta naphthylamide (ABNA), was inhibited by 10(-6)-10(-5) M of ME. This inhibition was abolished by verapamil, but not affected by naloxone. In the range of low concentrations ME appears to act on specific delta opioid receptors and its action is positively coupled to guanylate cyclase. In relatively higher concentrations ME-action is not mediated by specific delta opioid receptors and it appears to involve Ca2+ influx, adenylate cyclase activation as well as the processing of hormone by PM-enkephalinase.
...
PMID:Bidirectional effect of met-enkephalin on macrophage effector functions. 242 Nov 52

Rat thoracic aortic smooth muscle cells (line A10, ATCC CRL 1476) display a high density of atrial natriuretic factor (ANF) receptors. ANF stimulated the accumulation of cGMP in these cells in a time- and dose-dependent fashion. These cells are known to display a high density of vasopressin receptors of the vascular V1 subtype. These vasopressin receptors mediate inhibition of isoproterenol-stimulated cAMP accumulation and stimulation of inositol phosphate accumulation and calcium fluxes. Addition of [8-arginine]vasopressin ([Arg8]VP) to these cells inhibited ANF-stimulated cGMP accumulation. Inhibition of cGMP accumulation was dependent on the concentration of [Arg8]VP, with half-maximal and maximal effects occurring at 0.4 and 10 nM, respectively. [Arg8]VP did not have significant effects on basal cGMP levels. The inhibition by [Arg8]VP appears to be mediated by V1 receptors, since the V2 renal receptor agonist [1-desaminocysteine,8-D-arginine]vasopressin was ineffective. Also, the selective V1 antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-(O-methyltyrosine),8-arginine]vasopressin and the mixed V1/V2 antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-(O-ethyl-D-tyrosine),4-valine,8-arginine]vasopressin blocked the [Arg8]VP-mediated effect, whereas the selective V2 antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-D-isoleucine,4-valine,8-arginine]vasopressin was minimally effective. These data show that in rat aortic smooth muscle cells, V1 receptors are negatively coupled to guanylate cyclase. These data also suggest that the vasoconstrictor activity of [Arg8]VP might involve inhibition of ANF-receptor-mediated vascular relaxation through inhibition of cGMP accumulation in addition to its effects on isoproterenol-mediated cAMP accumulation and inositol phosphate accumulation and calcium fluxes.
...
PMID:Vasopressin-mediated inhibition of atrial natriuretic factor-stimulated cGMP accumulation in an established smooth muscle cell line. 243 Feb 90

Dynamic changes in total glucose utilization in isolated islets of Langerhans of the rat were determined by quantitation of the formation of 3H2O from D-[5-3H]glucose. The addition of 8-bromo-cGMP (8-Br-cGMP) or monobutyryl cGMP to the islets during a linear phase of glucose utilization resulted in concentration- and time-dependent increases in glucose utilization. Effects of the analogs of cGMP on glucose utilization were noted as early as 5 min after the onset of stimulation in the presence of 10 mM glucose. 8-Br-cGMP also increased the utilization of 1 mM glucose within 20 min. Stimulatory effects of 8-Br-cGMP were observed in the presence of cycloheximide or N-acetylglucosamine. Neither 8-bromo-cAMP (8-Br-cAMP) nor monobutyryl cAMP induced significant changes in glucose utilization at 1 or 10 mM glucose. In the presence of 3-isobutyl-1-methylxanthine (IBMX), 8-Br-cGMP, but not 8-Br-cAMP, induced a rapid change in glucose utilization. N-Methyl-N'-nitro-N-nitrosoguanidine, which activates guanylate cyclase, also stimulated glucose utilization in the presence of IBMX by 3-fold. IBMX alone did not change glucose utilization. In contrast, 8-Br-5'-GMP reduced glucose utilization, whereas 8-bromoinosine 3',5'-monophosphate and 8-bromoguanosine did not change glucose utilization. Sodium bromide did not affect glucose utilization. Glucose-stimulated insulin release was potentiated by 8-Br-cGMP, whereas insulin release from islets incubated in the absence of glucose or the presence of glyceraldehyde or 2-ketoisocaproic acid was not altered by 8-Br-cGMP. Thus, glucose utilization in pancreatic islets is modulated by cGMP, and the secretory response to 8-Br-cGMP is glucose dependent.
...
PMID:Effects of guanosine 3',5'-monophosphate on glucose utilization in isolated islets of Langerhans. 243 25

Atrial natriuretic peptide (ANP) stimulates cGMP production in isolated rabbit ventricular myocytes incubated in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine (1mM). Half maximal activation was found at 10(-8)M ANP. Cellular cGMP concentrations of around 0.6 pmol/10(6) cells were elevated 4-6 fold by ANP (10(-6)M), 3-4 fold by carbachol (1mM) and around 10 fold by sodium nitroprusside (1mM). ANP had no effect on basal or isoprenaline-stimulated cAMP concentrations or on basal or noradrenaline-stimulated turnover of phosphatidylinositol. From these results we conclude that ANP receptors, coupled to particulate guanylate cyclase, exist in cardiac ventricular muscle. This indicates that ANP may also have a physiological action on ventricular muscle contractility during volume expansion.
...
PMID:Actions of atrial natriuretic peptide (ANP) on cyclic nucleotide concentrations and phosphatidylinositol turnover in ventricular myocytes. 244 14

Effects of atrial natriuretic peptides (ANP) on the tension, content of guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate (cAMP) and activity of particulate and soluble forms of guanylate cyclase were examined in bovine tracheal smooth muscle. Atrial natriuretic factor (ANF), atriopeptin II, and atriopeptin III were found to induce relaxation of tracheal smooth muscle precontracted with 5 x 10(-8) M carbachol (an approximate median effective concentration) in a concentration-dependent manner. However, atriopeptin I failed to induce significant relaxation of the muscle. Similar results were obtained when 3 x 10(-6) M histamine or 5 x 10(-7) M serotonin was used as the contracting agent. However, the relaxant effects of ANF, atriopeptin II, and atriopeptin III were much less when a higher concentration of carbachol or 30 mM K+ was used as the contractile agent. Maximally inhibitory concentration (IC50) values of ANF, atriopeptin II, and atriopeptin III for inhibition of muscle contraction induced by 5 x 10(-8) M carbachol ranged from 3.8 to 8.3 x 10(-9) M, indicating that these peptides have intermediate potency between isoproterenol (IC50, 2.0 x 10(-9) M) and sodium nitroprusside (IC50, 2.0 x 10(-8) M). Treatment of the muscle with 3 x 10(-7) M ANF slowed the rate of tension development of the muscle by 10(-7) M carbachol. Tissue levels of cAMP were not influenced by any of the atrial peptides at concentrations of 10(-9)-10(-6) M; however, cGMP levels were increased about five- to ninefold.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:ANP relaxes bovine tracheal smooth muscle and increases cGMP. 246 7

Chondroprogenitor cells derived from avian tibia epiphyseal growth plate, and skin fibroblasts were cultured in vitro. In the fibroblasts, human (1-28) and rat (5-28) atrial natriuretic peptide (ANP) stimulated cyclic GMP (cGMP) production in a dose-dependent manner without affecting cAMP. Sodium nitroprusside also stimulated cGMP accumulation by chondroprogenitor cells and fibroblasts, but the maximum cGMP accumulation elicited by sodium nitroprusside was much lower than that obtained with ANP. The effects of ANP and sodium nitroprusside on chondroprogenitor cells and skin fibroblasts were additive. Human ANP increased cGMP production by the particulate fraction prepared either from chondroprogenitor cells or fibroblasts. Sodium nitroprusside, at concentrations of up to 1 mmol/l, did not affect cGMP production by the particulate fraction prepared from either cell type. The present study provides additional evidence that avian growth-plate chondroprogenitor cells and skin fibroblasts are targets for ANP. ANP and nitroprusside activate different guanylate cyclase isoenzymes--the particulate and soluble forms of the enzyme respectively. The data suggest that most of the guanylate cyclase activity in these cells is localized in the particulate fraction.
...
PMID:Atrial natriuretic peptide and sodium nitroprusside stimulate cyclic GMP accumulation by avian skin fibroblasts and epiphyseal growth-plate chondroprogenitor cells. 246 31

Escherichia coli heat-stable enterotoxins (ST) are classified into STa and STb according to their physicochemical and biologic characteristics. STa induces diarrhea, activating the guanylate cyclase-cGMP system. ST-like enterotoxins can be produced by bacteria other than E. coli, including Klebsiella pneumoniae. A Klebsiella ST has previously been shown to share some chemical and immunologic characteristics with E. coli ST. Aiming to define better the nature of Klebsiella ST, we have screened 237 children with diarrhea and 179 controls for ST-producing Klebsiella, using the SMA. We detected 26 Klebsiella strains from patients, two of which were positive in the SMA, and 36 from controls, all negative for ST. A partial purification was performed using an acetone precipitation followed by ultrafiltration and gel filtration techniques. Klebsiella toxin was heat-stable, methanol-soluble, sensitive to mercaptoethanol, active at acid pH values, but not at pH greater than 8. The time course of Klebsiella toxin in the SMA resembled that of E. coli STa. Klebsiella ST caused reduced Na absorption and net Cl secretion in rabbit ileal mucosa mounted in Ussing chambers. It was found to increase the cGMP but not the cAMP concentration. Finally, Klebsiella ST did not react with anti-E. coli STa MAb in a competitive ELISA. We conclude that K. pneumoniae may induce diarrhea through the production of an STa similar but not identical to E. coli STa.
...
PMID:Characteristics and mechanism of action of a heat-stable enterotoxin produced by Klebsiella pneumoniae from infants with secretory diarrhea. 247 15

It was found that a serotonin-induced decrease of the acetylcholine-induced chloride current in a group of right parietal ganglion neurons of the snail Helix pomatia was mimicked neither by dibutyryl cAMP nor by isobutyl methylxanthine. In contrast it was mimicked by the extracellular application of sodium nitroprusside as a guanylate cyclase activator, and by intracellular injection of cyclic guanosine monophosphate.
...
PMID:[Serotonin modulation of acetylcholine-induced currents in mollusk neurons as dependent on cyclic guanosine monophosphate]. 248 78

These studies were performed in vitro to investigate the nature of the second messenger for lower esophageal sphincter (LES) smooth muscle relaxation in response to electrical field stimulation (EFS) and vasoactive intestinal polypeptide (VIP). It was seen that VIP, permeant derivatives of the cyclic nucleotide 8-bromo cyclic GMP (BrcGMP) and 8-bromo cyclic AMP (8-BrcAMP), the guanylate cyclase stimulant sodium nitroprusside (SNP), the adenylate cyclase stimulant forskolin, M&B 22,948 (cGMP phosphodiesterase inhibitor) and SK&F 94,120 (cAMP phosphodiesterase inhibitor) caused dose-dependent and tetrocotoxin resistant fall in LES tension. Guanylate cyclase inhibitor methylene blue (MB) (3 x 10(-5) M), caused significant antagonism of fall in LES tension by SNP without modifying the inhibitory response of forskolin. The possible adenylate cyclase inhibitor N-ethylmaleimide (NEM) (1 x 10(-4) M), on the other hand, caused significant antagonism of fall in LES tension by forskolin without any effect on that caused by SNP. The inhibitory responses of 8-BrcGMP and 8-BrcAMP were not modified by MB or NEM. NEM (1 x 10(-4) M) and MB (3 x 10(-5) M) caused significant inhibition of the fall in LES tension with EFS. NEM also caused inhibition of fall in LES tension by VIP. Furthermore, SK&F 94,120 and not M&B 22,948 caused significant potentiation of fall in LES tension by EFS. From these results we conclude that: 1) cAMP and cGMP may act as second messengers for LES relaxation with EFS and VIP, and 2) VIP may act primarily via cAMP system and remains a strong possibility for one of the inhibitory neurotransmitters in the LES.
...
PMID:Influence of stimulators and inhibitors of cyclic nucleotides on lower esophageal sphincter. 253 11


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---