Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, an ANF-sensitive guanylate cyclase (GC-A) has been cloned from a rat brain cDNA library. Here we studied the stimulation of cyclic GMP accumulation in response to atrial natriuretic factor (ANF), urodilatin and atriopeptin I (AP-1) in a rat glioma C6 cell line permanently transfected with GC-A as well as GC-A activity in membranes from these C6 cells and in membranes from COS-7 cells that were transiently transfected with GC-A. We also measured binding affinities for these natriuretic peptides in the membrane preparations. These characteristics of GC-A were compared to those of membrane preparations from adrenal cortex of bovine and human origin. The order of potency of stimulation of cyclic GMP accumulation in permanently transfected glioma cells was ANF greater than urodilatin greater than AP I; AP I stimulated cyclic GMP accumulation. A similar order of potency was obtained for stimulation of guanylate cyclase activity in membranes from permanently transfected glioma cells as well as from transiently transfected COS-7 cells. In contrast, AP-1 was uneffective to stimulate guanylate cyclase in membrane preparations from adrenal cortex from bovine as well as from human origin. Furthermore, urodilatin was equipotent to ANF in these preparations. Binding affinities were comparable for ANF and urodilatin in membranes from cells transfected with GC-A and in membranes from adrenal cortex of both sources, whereas AP-1 had a weaker affinity in all preparations studied.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of a cloned ANF-sensitive guanylate cyclase (GC-A) with particulate guanylate cyclase from adrenal cortex. 134 56

1. The vasoconstrictor peptide endothelin-1 caused a fast, transient rise in guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels in a neuronal cell line (mouse neuroblastoma x rat glioma hybrid cells 108CC15). The mechanism of activation of guanylate cyclase by endothelin-1 was investigated. The endothelin-1-induced rise depended on the release of internal Ca2+. 2. The stimulation of cyclic GMP synthesis induced by endothelin-1 was suppressed after preincubating the cells in medium containing haemoglobin (IC50 3 microM). Similarly, pretreatment of the cells with the L-arginine analogues, L-canavanine (IC50 60 microM) or NG-monomethyl-L-arginine (IC50 2.5 microM), inhibited the cyclic GMP response to endothelin-1. Therefore, endothelin-1 activates guanylate cyclase most probably via formation of nitric oxide, which is released from L-arginine. 3. The Ca2+ ionophore ionomycin induced a transient rise in cyclic GMP levels, which was also suppressed by preincubation in the presence of either haemoglobin or the L-arginine analogues L-canavanine or NG-monomethyl-L-arginine. Therefore, we conclude that ionomycin can activate guanylate cyclase by a mechanism involving nitric oxide formation, similar to that induced by endothelin-1. 4. The alkaloid veratridine, which activates Na+ channels and also causes influx of Ca2+ induced a transient rise of cyclic GMP levels in the neuronal cell line. This stimulation was blocked by pretreating the cells with L-canavanine, NG-monomethyl-L-arginine or haemoglobin. 5. Loading the cells with the Ca2+ chelator BAPTA suppresed the cyclic GMP response to application of endothelin-1, ionomycin, or veratridine. Thus, in the neuronal cell line a rise in cytosolic Ca2 + activity seems to be sufficient to stimulate the nitric oxide forming enzyme which synthesizes the activator of soluble guanylate cyclase.
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PMID:Endothelin and a Ca2+ ionophore raise cyclic GMP levels in a neuronal cell line via formation of nitric oxide. 196 7

Atrial natriuretic factors (ANFs) were tested for their effects on cyclic GMP production in two neurally derived cell lines, the C6-2B rat glioma cells and the PC12 rat pheochromocytoma cells. These cell lines were selected because both are known to possess high amounts of the particulate form of guanylate cyclase, a proposed target of ANF in peripheral organs. Previous studies from our laboratory have shown that ANF selectively activates particulate, but not soluble, guanylate cyclase in homogenates of a variety of rat tissues and that one class of ANF receptor appears to be the same glycoprotein as particulate guanylate cyclase. In the present study we found that four analogs of ANF stimulate cyclic GMP accumulation in both C6-2B and PC12 cells with the rank order of potency being atriopeptin III = atriopeptin II greater than human atrial natriuretic polypeptide greater than atriopeptin I. Atriopeptin II (100 nM) for 20 min elevated cyclic GMP content in C6-2B cells fourfold and in PC12 cells 12-fold. Atriopeptin II (100 nM) for 20 min also stimulated the efflux of cyclic GMP from both C6-2B cells (47-fold) and PC12 cells (12-fold). Accumulation of cyclic GMP in both cells and media was enhanced by preincubation with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (250 microM). After 20 min of exposure to atriopeptin II, cyclic GMP amounts in the media were equal to or greater than the amounts in the cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Atrial natriuretic factors stimulate accumulation and efflux of cyclic GMP in C6-2B rat glioma and PC12 rat pheochromocytoma cell cultures. 243 84

Serotonin (5-HT) induced a transient rise of the cyclic GMP level in neuroblastoma X glioma hybrid cells, half-maximally at 1 microM 5-HT. 2-Methyl-5-HT displayed an about 5 times lower potency but equal efficacy. alpha-Methyl-5-HT and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) were completely ineffective at concentrations up to 30 microM. Antagonists specific for 5-HT3 receptors, ICS 205-930, GR 38032 F and MDL 72222, blocked the response to 5-HT at nanomolar concentrations but antagonists directed towards 5-HT1 and 5-HT2 receptors, ketanserin and methysergide, had no effect at concentrations up to 1 microM. Thus, 5-HT3 receptors are responsible for activating guanylate cyclase in the hybrid cells.
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PMID:Serotonin raises the cyclic GMP level in a neuronal cell line via 5-HT3 receptors. 254 82

The growth of C6 glioma and L1210 leukemic cells has been stimulated in serum-free medium by the addition or iron or transferrin. The growth promoting action of transferrin was lost when iron was chelated in the culture medium using desferrioxamine. L1210 cells can be grown continuously in serum-free medium supplemented with transferrin or FeCl3 only. In this latter case, it has been shown that L1210 cells secrete into the medium some factor which facilitates iron uptake. The growth of L1210 cells in their exponential phase was blocked by desferrioxamine at the G1-S interface of the cell cycle. The action of transferrin on cell growth was also inhibited by propyl gallate - a known antioxidant which prevents lipid peroxidation. The action of iron was more potent than hemin in reversing the influence of propyl gallate on L1210 cell growth. Iron was found to activate purified guanylate cyclase in the presence of unsaturated fatty acids. This suggests that cyclic GMP synthesis could be involved in the promotion of transformed cell growth by iron.
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PMID:Growth promotion of transformed cells by iron in serum-free culture. 285 72

The cellular cGMP content increased in response to a variety of receptor agonists, which activate [e.g., prostaglandin (PG) E1, E2, and F2 alpha] or inhibit (e.g., alpha-adrenergic, muscarinic, and opiate agonists) adenylate cyclase in neuroblastoma X glioma hybrid NG108-15 cells. The responses were additive when PGF2 alpha and enkephalin were mixed. The inhibitory guanine nucleotide regulatory protein (Ni) is involved in adenylate cyclase inhibition; this function of Ni is lost when it is ADP-ribosylated by islet-activating protein (IAP), pertussis toxin [H. Kurose, T. Katada, T. Amano, and M. Ui (1983) J. Biol. Chem. 258, 4870-4875]. The cGMP rise induced by stimulation of the receptors linked to adenylate cyclase inhibition was also diminished by IAP; the time course and dose response for the IAP-induced diminution were the same between adenylate cyclase inhibition and cGMP generation. Ni thus appears to mediate guanylate cyclase activation as well as adenylate cyclase inhibition initiated via the same receptors. Melittin also increased cGMP. No additivity was shown when enkephalin and melittin were combined, suggesting that phospholipase A2 might play a role in Ni-mediated guanylate cyclase activation. On the other hand, the PGF2 alpha-induced cGMP rise was associated with increased incorporation of 32Pi into phosphatidylinositol; was not affected by cholera toxin, IAP or forskolin; and showed no additivity when combined with A23187, which increased cGMP by itself. PGs would occupy receptors linked to phosphatidylinositol breakdown, thereby increasing the availability of intracellular Ca2+, which is responsible for guanylate cyclase activation. Thus, dual pathways are proposed for a receptor-mediated cGMP rise in NG108-15 cells.
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PMID:Dual pathways of receptor-mediated cyclic GMP generation in NG108-15 cells as differentiated by susceptibility to islet-activating protein, pertussis toxin. 298 51

It has been shown recently that astroglial cells of the mammalian CNS possess receptors for neurotransmitters. In order to analyze what sequences of cellular events occur upon activation of these glial receptors, we utilized a 5-HT receptor in a rat clonal cell of glial origin as a model system. When the C6BU-1 glioma cells were exposed to 5-HT, the cytosolic Ca2+ concentration ([Ca2+]i) was elevated and the cellular content of cGMP was increased in a dose-dependent manner. 5-HT receptor antagonists and a Ca2+ entry blocker suppressed the increases in both [Ca2+]i and cGMP. The magnitude of the cGMP increment depended on the environmental Ca2+ concentration and was totally blocked by Ca2+ depletion. Application of a Ca2+ ionophore increased [Ca2+]i and cGMP. There was a tendency for extremely high [Ca2+]i to suppress the cGMP increment. On the contrary, membrane-permeable cyclic nucleotide analogs failed to increase [Ca2+]i. These results suggest that the following sequence of events occurs in 5-HT-induced C6BU-1 cells: activation of 5-HT receptors, Ca2+ influx, a rise in [Ca2+]i, activation of guanylate cyclase, and, finally, activation of cyclic nucleotide phosphodiesterase.
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PMID:Cytosolic calcium elevation and cGMP production induced by serotonin in a clonal cell of glial origin. 301 93

Guanylate cyclase was activated 3- to 10-fold by hemin in a dose-dependent manner in membranes prepared from homogenates of rat lung, C6 rat glioma cells, or B103 rat neuroblastoma cells. Maximum activation was observed with 50 to 100 microM hemin with higher concentrations being inhibitory. Activation was observed when Mg2+-GTP but not when Mn2+-GTP was used as the substrate. Increased enzyme activity reflected selective activation of the particulate form of guanylate cyclase; hemin inhibited the soluble form of guanylate cyclase 70 to 90% over a wide range of concentrations. Activation was not secondary to proteolysis since a variety of protease inhibitors failed to alter stimulation by hemin. Protophorphyrin IX had little effect on particulate guanylate cyclase activity and sodium borohydride almost completely abolished hemin-dependent activation. These data suggest a requirement for the ferric form of the porphyrin-metal chelate for activation. However, agents which interact with the iron nucleus of porphyrins, such as cyanide, had little effect on the ability of hemin to activate guanylate cyclase. The stimulatory effects of hemin were observed in the presence of detergents such as Lubrol-PX, and highly purified particulate enzyme could be activated to the same extent as enzyme in native membranes. These data suggest that the interaction of porphyrins with particulate guanylate cyclase is complex in nature and different from that with the soluble enzyme.
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PMID:Selective activation of particulate guanylate cyclase by a specific class of porphyrins. 614 94

Addition of GM3 (10(-7) or 5.10(-5) M) did not affect the specific activity of adenyl and guanyl cyclase in confluent cultures of C6 glioma cells. Higher concentrations inhibit the cyclases.
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PMID:[Effect of GM3 ganglioside on the adenyl and guanyl cyclase activity of cultured cells]. 615 47

We studied the activity and the ultracytochemical localization of membrane-bound guanylate cyclase (GC) after stimulation with rat atrial natriuretic peptide (rANP), porcine brain natriuretic peptide (pBNP), rat brain natriuretic peptide (rBNP), or porcine C-type natriuretic peptide (CNP) in rat C6 glioma cells during proliferation or following exposure of confluent cells to dibutyryl cyclic AMP (db-cAMP) or retinoic acid (RA). Under our experimental conditions all peptides were activators of GC as demonstrated by the accumulation of cGMP within cells. During proliferation of C6 cells, the amounts of cGMP remained approximately constant. However, at subconfluency, confluency and postconfluency, the GC reaction product was located at different sites in C6 cells. At subconfluency, GC reaction product was on membranes of protoplasmic extensions, at postconfluency, GC reaction product was in association with membranes of cell bodies, and at confluency, both localizations of GC reaction product were detected. Incubation of confluent cells in culture medium containing db-cAMP or RA induced the appearance of long and slender protoplasmic extensions. Under these conditions, the GC reaction product was localized exclusively to these processes. These data suggest that GC is differentially located depending on the state of growth of glial cells, and that in differentiating glial cells GC is preferentially located in cell processes.
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PMID:Detection of membrane-bound guanylate cyclase activity in rat C6 glioma cells at different growth states following activation by natriuretic peptides. 755 44


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