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)

Specific binding of iodinated natriuretic peptides 125I-ANP and 125I-CNP was examined in the gill of the Atlantic hagfish Myxine glutinosa by tissue section autoradiography, saturation and competition analysis of binding to membrane preparations, affinity cross-linking, followed by SDS-PAGE and guanylate cyclase assays. Autoradiographs showed specific, saturable binding on the respiratory lamellar epithelium. In vitro analysis of the binding sites demonstrated that 125I-ANP bound to two receptor sites with the same affinity (Kd = 15.4 +/- 1.6 pmol l-1; Bmax = 45.9 +/- 3.0 fmol mg-1 protein). 125I-CNP bound to high- and low-affinity receptor sites; variables for the high-affinity site (Kd = 12.9 +/- 4.7 pmol l-1; Bmax = 23.4 +/- 6.5 fmol mg-1 protein) did not differ from those for the 125I-ANP sites. The low-affinity site had an apparent Kd and Bmax of 380 +/- 80 pmol l-1 and 120 +/- 21 fmol mg-1 protein, respectively. All receptors had an apparent molecular mass of approximately 150 kDa, with no indication of a mammalian type NPR-C at a lower apparent molecular mass. 1 nmol l-1 unlabelled rANP and 20 and 30 nmol l-1 unlabelled pCNP and C-ANF, respectively, competed for 50% of 125I-ANP sites. 0.1 nmol l-1 rANP and pCNP and 8 nmol l-1 C-ANF competitively inhibited 50% of 125I-CNP binding. Both rANP and pCNP stimulated cyclic GMP production, although rANP was a more potent stimulator than was pCNP. C-ANF did not stimulate cyclic GMP production. These data suggest the existence of an ANP guanylate-cyclase-linked receptor similar to the mammalian NPR-A and an ANP/CNP receptor that may be similar to, although not structurally homologous with, the mammalian NPR-C clearance receptor.
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PMID:Localisation and characteristics of natriuretic peptide receptors in the gills of the Atlantic hagfish Myxine glutinosa (Agnatha). 789 Oct 31

The membrane-bound form of guanylate cyclase represents a biologically active atrial natriuretic factor receptor (GC/ANF-R). We have constructed genomic map of murine GC-A/ANF-R gene using 17 different restriction endonucleases. The restriction mapping results indicated that murine GC-A/ANF-R gene is approximately 20 kb single copy with multiple smaller exons and bigger introns. The Kpn I and Sfu I restriction digests produced 27 kb and 35 kb fragments, respectively, which hybridized with 5'- and 3'-flanking cDNA probes. Both of these fragments should cover the entire murine GC-A/ANF-R genomic sequences. The southern blot hybridization of genomic DNA from human, rat and mouse, using murine 5'-flanking cDNA probe indicated the presence of higher variant sequences in the 5'-flanking region of GC-A/ANF-R gene among different species. The noncoding 5'-flanking probe (350 bp) hybridized only to mouse genomic DNA but not to the human or rat DNA. These sequence variations located in the noncoding 5'-flanking region of GC-A/ANF-R gene may explain the divergent evolutionary development among different species. This is the first demonstration of the restriction endonuclease digestion and genomic mapping of murine GC-A/ANF-R gene which should be valuable to the understanding of its regulation and function.
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PMID:Genomic restriction endonuclease analysis and mapping of murine guanylate cyclase-A/atrial natriuretic factor receptor gene. 790 87

We examined the effects of C-type natriuretic peptide (CNP) on cyclic GMP production and catecholamine synthesis in cultured bovine adrenal medullary cells. 1) CNP increased intracellular cyclic GMP content in a concentration-dependent manner (10-1000 nM). 2) The cyclic GMP production induced by 1 microM CNP reached a 200-fold increase, and the effect of CNP was most potent among the natriuretic peptide family. 3) The CNP-induced cyclic GMP production was attenuated by endothelin (1 microM) and angiotensin II (0.1-1 microM). 4) When the cells were cultured with hypertonic NaCl medium, the CNP-induced cyclic GMP production was potentiated in a time (1-4 days)- and concentration (25-100 mM)-dependent manner. 5) CNP stimulated the synthesis of 14C-labeled catecholamines from [14C] tyrosine but not from [14C] dopa. The stimulatory effect of CNP on the 14C-labeled catecholamine synthesis was observed at the concentrations of 100 to 100 nM. 6) 8-Bromo cyclic GMP, a membrane-permeable cyclic GMP analog, and sodium nitroprusside, an activator of soluble guanylate cyclase, also stimulated the synthesis of 14C-labeled catecholamines from [14C]tyrosine, whereas C-ANF, a specific ligand for the ANP-C (clearance) receptor that does not increase cyclic GMP content, failed to stimulate the synthesis of 14C-labeled catecholamines. 7) CNP (1 microM) as well as 8-bromo cyclic GMP and sodium nitroprusside increased the activity of tyrosine hydroxylase in the cells. These results suggest that in the adrenal medulla, CNP is a potent agonist for cyclic GMP production, which is modulated by endothelin, angiotensin II and the hypertonic NaCl condition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:C-type natriuretic peptide stimulates catecholamine synthesis through the accumulation of cyclic GMP in cultured bovine adrenal medullary cells. 790 32

Mastoparan potently stimulated catalytic activity of guanylate cyclase-coupled atrial natriuretic factor receptor (GC-A/ANF-R), both in the plasma membranes and intact Leydig tumor (MA-10) cells. In plasma membrane preparations, a maximum of 5-fold GC catalytic activity was stimulated by 100 microM mastoparan and the half maximum stimulation (EC50) was achieved at 40 microM concentration. Mastoparan potentiated GC activity by more than 40%, above the level, stimulated by ANF. Mas 7, an active analog of mastoparan, stimulated the GC activity in a similar manner to mastoparan whereas Mas 17, an inactive analog, did not enhance GC activity. In membranes prepared from mastoparan-treated intact MA-10 cells, GC catalytic activity was enhanced by more than 4-fold as compared with untreated control cells. Pretreatment of membranes with either anti-Gs alpha or anti-Gi alpha antibodies had no effect on mastoparan-stimulated GC activity, however, anti-Go alpha antibodies inhibited the stimulatory effect of mastoparan by almost 50%. Agents known to modulate the effect of mastoparan such as EGTA (Ca2+ chelator), W7 (calmodulin inhibitor) and staurosporine (protein kinase C inhibitor) had no effect on the mastoparan-stimulated GC activity. Mastoparan enhanced the ANF-stimulated GC activity in detergent solubilized membrane preparations without a significant change in ANF-binding capacity. The data establish a role for mastoparan in the ANF-dependent stimulation of GC-A/ANF-R catalytic activity, both in the plasma membrane preparations and intact Leydig tumor (MA-10) cells. Furthermore, these findings provide new evidence that mastoparan (isolated from wasp venom) potently stimulates guanylate cyclase activity of GC-A/ANF-R by activating G-proteins.
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PMID:Modulation of guanylate cyclase-coupled atrial natriuretic factor receptor activity by mastoparan and ANF in murine Leydig tumor cells: role of G-proteins. 794 43

The membrane-bound form of guanylate cyclase/atrial natriuretic factor receptor (GC/ANF-R) is a 135 kDa transmembrane glycoprotein which binds ANF with high affinity. We have expressed the extracellular ligand-binding domain of murine guanylate cyclase ANF-R (GC/ANFR-LBD) cDNA in Escherichia coli. The cDNA encoding the extracellular ANF-binding domain (nucleotide positions covering from 432-1755 base pair) of GC/ANF-R was amplified by polymerase chain reaction, cloned into BamHI site of pGEX-3X prokaryotic expression vector and was transfected into E. coli, strain JM101. After isopropyl-beta-D-thiogalactopyranoside (IPTG) induction of bacterial cells, the GC/ANFR-LBD was expressed as the glutathione-S-transferase (GST) fusion protein, yielding a molecular mass of 70 kDa. The expressed fusion protein was characterized for binding affinity to both full length and truncated ANF molecules. After expression in E. coli, the binding of 125I-ANF to the extracellular region of GC/ANF-R was similar and corresponded to the pharmacological class of native receptor protein. The 70 kDa fusion product was purified as a predominant single protein band by glutathione-affinity chromatography. These findings establish that E. coli may be utilized as an effective heterologous model system to delineate the structure-function analysis of guanylate cyclase-coupled ANF receptor molecules.
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PMID:Expression of extracellular ligand-binding domain of murine guanylate cyclase/atrial natriuretic factor receptor cDNA in Escherichia coli. 809 55

The membrane-bound form of guanylate cyclase represents a biologically active atrial natriuretic factor receptor (GC/ANF-R). Murine Leydig tumor (MA-10) cells predominantly overexpress GC/ANF-R in high density (Pandey, K. N., Pavlou, S. N., and Inagami, T. (1988) J. Biol. Chem. 263, 13406-13413; Pandey, K. N., and Singh, S. (1990) J. Biol. Chem. 265, 12342-12348). Information regarding the post-binding events of GC/ANF-R is obscure. This study presents the kinetics of internalization, recycling, and redistribution of GC/ANF-R in model MA-10 cells. Both the 125I-ANF binding assays and photoaffinity labeling procedures were utilized to label the total, intracellular, and cell surface GC/ANF-R. After the binding of 125I-ANF to GC/ANF-R, this complex was internalized and both the intact and degraded ligands were released into culture media. The distribution of 125I-ANF on the cell surface, in the intracellular compartments, and into culture media provided a dynamic relationship between the rates of 125I-ANF uptake, its degradation, and extrusion. The extent of receptor recycling was measured using tryptic proteolysis of photoaffinity-labeled GC/ANF-R to distinguish cell surface receptors from those that were internalized. A population of GC/ANF-R rapidly recycled (t1/2 = 5 min) from intracellular compartment to plasma membrane. Recycling of GC/ANF-R was impaired by chloroquine, dinitrophenol, and low temperature (22 degrees C). Furthermore, these studies suggest that dissociation of ANF from the receptor is not required for recycling of internalized GC/ANF-R.
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PMID:Stoichiometric analysis of internalization, recycling, and redistribution of photoaffinity-labeled guanylate cyclase/atrial natriuretic factor receptors in cultured murine Leydig tumor cells. 809 48

Recent molecular cloning reports show that there are at least three membrane guanylate cyclases in vertebrate retina: (1) atrial natriuretic factor receptor guanylate cyclase (ANF-RGC), (2) C-type natriuretic peptide receptor guanylate cyclase (CNP-RGC), and (3) "retinal guanylate cyclase" (RetGC). The specific cellular localization of the first two cyclases is unknown, but RetGC is apparently localized in photoreceptor cells, suggesting that it participates in visual transduction. With the overall objective of identifying the guanylate cyclase that is linked to phototransduction, we compared the structural and regulatory properties of the biochemically characterized 112 kDa bovine rod outer segment membrane guanylate cyclase (ROS-GC) with those of RetGC, ANF-RGC and CNP-RGC. The N-terminal and two internal peptide sequences of purified ROS-GC had about 90% similarity with the corresponding sequences of the RetGC; the sequence identity with natriuretic peptide receptor cyclases was about 30%. A 19 amino acid long sequence from a tryptic peptide of ROS-GC had no corresponding sequence in the other three cyclases. ROS-GC was inhibited by ATP but ANF-RGC and CNP-RGC were activated by ATP in the presence of the respective peptide hormones. These results suggest that ROS-GC represents a new subtype of the membrane guanylate cyclase family that is structurally and biochemically distinct from the other retinal cyclases.
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PMID:Structural and biochemical identity of retinal rod outer segment membrane guanylate cyclase. 810 54

An ANF-like material was detected by radioimmunoassay in the isolated perfused rabbit kidney. The production of ANF-like material after 90 min of perfusion under hypoxia was 3000 pg/ml vs 500 pg/ml under normoxia or control conditions. This material is partially inactivated by heat treatment at 100 degrees C for 5 min and is absorbed on a SEP-PAK column (C18, Waters) but, unlike ANF, cannot be recovered from the column. On Sephadex G25 chromatography, elution in water yielded two active fractions, one corresponding to the solvent front and the second obtained after one column volume. Four fractions with biological activity were eluted with water from Sephacryl 200. Several fractions were tested on rabbit aorta preconstricted with 1 microM phenylephrine, without removal of endothelial cells. Treatment of T84 cells in culture by the crude material promoted a dose-related increase (1:2, 1:5, 1:10) of the generation of cyclic GMP. In contrast to our material, ANF (atriopeptin III, 1 microM-10 fM) failed to activate guanylate cyclase in T84 cells, while the heat-stable E. coli enterotoxin (STa) significantly increased cyclic GMP levels at the dose of 5 microM. We propose that a new ANF/urodilatin/ST-like material was generated by the hypoxic kidney under perfusion, which we name FNS (Factor Natriureticus Similis).
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PMID:Partial characterization of an ANF/urodilatin-like substance released from perfused rabbit kidney under hypoxia. 822 Feb 71

In this study we compared the levels and responsiveness of atrial natriuretic peptide (ANP) receptors in neuronal and astrocyte glial cultures from spontaneously hypertensive (SH) and normotensive (Wistar-Kyoto: WKY) rat brain. Both neuronal and astrocyte glial cultures from the hypothalamus and brain stem of 1-day-old SH and WKY rats display specific high-affinity binding sites for 125I-labeled ANP. The presence of a large population of ANP-C receptors in each type of culture is indicated by the strong competition of 125I-ANP binding by the ring-deleted analogue of ANP [C-ANF-(4-23)]. In neuronal cultures from both strains, C-type natriuretic peptide (CNP-22) was the most effective natriuretic peptide in stimulating guanosine 3',5'-cyclic monophosphate (cGMP) levels, suggesting the presence of ANP-B receptors in these cells. By contrast, ANP was the most effective stimulator of cGMP levels in SH and WKY rat astrocyte glial cultures, suggesting the presence of ANP-A receptors. Here, we have determined that there is a decrease in the maximum binding capacity for 125I-ANP-specific binding in both SH rat neuronal and astrocyte glial cultures compared with their respective control cells. The stimulatory effects of CNP-22 on cGMP levels in SH rat neurons and of ANP on cGMP levels in SH rat astrocytes were significantly reduced compared with their respective WKY rat cultures. Our data suggest that the lower number of ANP receptors in SH rat neuronal and astrocyte glial cultures includes a reduction in the guanylate cyclase-coupled ANP receptors.
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PMID:ANP receptors in neurons and astrocytes from spontaneously hypertensive rat brain. 839 76

Adipose tissue of the mesenteric territory contains large quantities of natriuretic peptide receptors (NPR) mainly of the NPR-C subtype. Guanylyl cyclase-bound receptors are also present since atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) are equally potent in activating this enzyme. While searching for a potential biological role for NP in adipocytes we observed that ANP-mediated generation of cyclic GMP (cGMP) was potentiated when the cells were simultaneously treated with isoproterenol. Indeed, isoproterenol, a beta-adrenergic agonist, and forskolin, an activator of adenylyl cyclase, can both double or triple cGMP production in response to ANF stimulation. There was a direct correlation between the level of cyclic AMP (cAMP) generated and the level of NP-mediated cGMP production suggesting that a cAMP-dependent mechanism may be responsible of this potentiation. To determine whether or not this phenomenon was unique to adipocytes, NPR subtypes were characterized in 4 established cell lines and their cAMP-dependent cGMP behavior examined. A10 and A7r5 smooth muscle cells showed identical ratio of NPR subtypes with about 95% NPR-C and 5% NPR-B. PC12 cells presented 100% NPR-A and NIH 3T3 fibroblasts 50% NPR-C and 50% NPR-B. Regardless of the NPR subtype, forskolin could not potentiate the cGMP generation in these cell lines. These data indicate that the cAMP-dependent potentiation of the NP-mediated cGMP production is unique to adipocytes, appears independent of the guanylyl cyclase-linked NPR subtypes and may be involved in the sensitization of the guanylyl cyclase domain of NPR for a potential biological role of NP in the adipose tissue.
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PMID:Specific potentiation by cyclic AMP of natriuretic peptide-mediated cyclic GMP production in adipose tissue. 864 24


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