Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preincubation of 1321N1 human astrocytoma cells in medium buffered with bicarbonate induced 50 to 100% increases in subsequent stimulation of cyclic AMP accumulation by the beta adrenergic receptor agonist isoproterenol and by the direct adenylyl cyclase activator forskolin, compared to cells incubated in buffered medium without bicarbonate. This "bicarbonate-induced sensitization" of cyclic AMP accumulation occurred rapidly, was rapidly reversible and was bicarbonate concentration-dependent. Although protein kinase C activation also induces sensitization in these cells, sensitization by bicarbonate does not appear to involve protein kinase C, because neither protein kinase C down-regulation nor the kinase inhibitor staurosporine prevented sensitization. Pertussis toxin neither mimicked nor prevented the sensitization by bicarbonate, suggesting that pertussis toxin-sensitive guanine nucleotide-binding proteins are not involved. The effect of bicarbonate appears to be on synthesis of cyclic AMP rather than degradation, inasmuch as the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine did not prevent expression of sensitization and because cyclic AMP degradation rates were not altered after bicarbonate incubation. However, increased adenylyl cyclase activity was not retained in broken cell preparations from cells incubated with bicarbonate. These results suggest the occurrence of a novel mechanism through which bicarbonate exposure can regulate adenylyl cyclase activity in intact cells.
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PMID:Bicarbonate induces sensitization of cyclic AMP accumulation by intact 1321N1 human astrocytoma cells. 768 Jul 17

The recent isolation and cloning of the G protein-coupled central cannabinoid receptor (CB1) from brain tissue has provided a molecular basis to elucidate how cannabinoid compounds may mediate their psychoactive effects. Here we report the high expression of cannabinoid receptors in human astrocytoma tumors of different grades, in the astrocytoma cell lines U373 MG and GL-15, as well as in normal astrocytes. From an analysis of the coupling mechanisms of functional CB1 receptors in U373 MG, we show that, in addition to the inhibition of adenylyl cyclase, activation by the cannabinoid agonist CP-55940 induces the expression of the immediate-early gene krox-24, also known as NGFI-A, zif/268, egr-1, and TIS8. The amount of Krox-24 protein and the level of Krox-24 DNA binding activity, as measured by Western blot and electrophoretic mobility shift assay, respectively, were also increased by the addition of CP-55940. These effects were blocked by incubation with pertussis toxin but not by treatment with hydrolysis-resistant cAMP analogues, suggesting that the transduction pathway between the cannabinoid receptor and krox-24 involves a pertussis toxin-sensitive GTP-binding protein and is independent of cAMP metabolism. The specific involvement of CB1 in Krox-24 induction was demonstrated in Chinese hamster ovary cells transfected with the human CB1 receptor and also in experiments using the CB1-selective cannabinoid antagonist SR 141716A.
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PMID:Stimulation of cannabinoid receptor CB1 induces krox-24 expression in human astrocytoma cells. 777 59

Rat C6 astroglioma cells (C6-bH1R cells) expressing cloned bovine histamine H1 receptors were established by transfection with a vector (pEF-BOS-bH1R) which carried a 2.7-kbp EcoRI fragment of the bovine H1 receptor cDNA [Yamashita, M. et al. (1991) Proc. Natl. Acad. Sci. USA 88, 11515-11519]. The cloned bovine H1 receptor in C6-bH1R cells was characterized by three established criteria: the [3H]mepyramine binding assay, the accumulation of inositol phosphates induced by histamine, and histamine-induced elevation of intracellular Ca2+ concentration ([Ca2+]i). The accumulation of inositol phosphates induced by histamine was time- and dose-dependent. The accumulation of inositol trisphosphate was biphasic with a prompt increase to the maximal level, followed by a sustained submaximal level. The histamine-induced accumulation of inositol phosphates was suppressed by phorbol ester, but not by pertussis toxin. Results from the [3H]-mepyramine binding assay and histamine-induced elevation of [Ca2+]i were characteristic of H1 receptors. Several compounds among tricyclic antidepressants, neuroleptics, and serotonin antagonists showed affinities to the cloned bovine H1 receptor with Ki values similar to reported values. Histamine neither induced cAMP accumulation nor attenuated forskolin-induced cAMP accumulation in C6-bH1R cells. C6-bH1R cells are particularly useful for studying the H1 receptor-mediated astroglial cell functions.
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PMID:Expression and characterization of the bovine histamine H1 receptor in cDNA-transfected C6 astroglioma cells. 798 97

1. The effect of mastoparan, a wasp venom toxin, on intracellular free Ca2+ concentration ([Ca2+]i) was examined in human astrocytoma cells. Mastoparan inhibited [Ca2+]i induced by carbachol (100 microM) in a concentration-dependent manner in the absence of extracellular Ca2+, consistent with our previous results showing that mastoparan inhibits phosphoinositide hydrolysis in human astrocytoma cells. 2. In contrast, mastoparan itself increased [Ca2+]i and augmented carbachol-induced increase in the [Ca2+]i in the presence of extracellular Ca2+, suggesting that mastoparan elicited Ca2+ influx from the extracellular medium. The increase appeared to be maximum at extracellular Ca2+ concentrations of 0.1-0.2 mM. The higher concentrations of extracellular Ca2+ depressed the influx. 3. Pertussis toxin did not affect mastoparan-induced inhibition of [Ca2+]i in the absence of extracellular Ca2+, consistent with the previous results that pertussis toxin did not affect mastoparan-induced inhibition of phosphoinositide hydrolysis. 4. Pertussis toxin augmented mastoparan-induced increase in [Ca2+]i in the presence of extracellular Ca2+, suggesting that pertussis toxin substrate(s) seems to be inhibitory for Ca2+ influx induced by mastoparan. 5. Verapamil, nifedipine and diltiazem (each 10 microM), L-type Ca2+ antagonists, did not affect mastoparan-induced Ca2+ influx. However, verapamil (10 microM) slightly inhibited the increase in [Ca2+]i induced by carbachol in the presence of mastoparan. 6. The results obtained in the present study indicate that mastoparan has two opposite effects on [Ca2+]i in human astrocytoma cells and possibly has at least two sites of action.
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PMID:Dual effects of mastoparan on intracellular free Ca2+ concentrations in human astrocytoma cells. 803 54

P2Y purinergic receptors previously have been shown to couple either to activation of phospholipase C through a pertussis toxin-insensitive mechanism or to inhibition of adenylyl cyclase through pertussis toxin-sensitive members of the G1 family of G proteins. These and other pharmacological data strongly suggest that multiple P2Y purinergic receptors exist. Webb et al. [FEBS Lett. 324:219-225 (1993)] cloned a cDNA that, when expressed in frog oocytes, displayed the general pharmacological characteristics of a P2Y purinergic receptor but whose second messenger linkage was not resolved. We have now cloned the meleagrid (turkey) homologue of the previously cloned chick P2Y purinergic receptor and have stably expressed it in a heterologous human cell line (1321N1 astrocytoma cells) to establish its signaling properties. The purinergic receptor agonist 2-methylthio-ATP (2MeSATP) stimulated a marked activation of phospholipase C in 1321N1 cells stably expressing the meleagrid receptor. The order of potency of a series of analogues of ATP and ADP for stimulation of phospholipase C by the receptor expressed in 1321N1 cells [2MeSATP = 2-methylthio-ADP > adenosine 5'-O-(2-thio)diphosphate > ADP > 2-chloro-ATP = adenosine 5'-O-(3-thio)triphosphate > or = ATP > adenylyl-imidodiphosphate > UTP] was similar to that observed for P2Y purinergic receptors in turkey erythrocytes and many other tissues and was markedly different from those of the P2U and P2X purinergic receptor subtypes. Stimulation of inositol lipid hydrolysis by P2Y purinergic agonists was not affected by preincubation of cells with pertussis toxin. In contrast to its marked effects on phospholipase C activity, 2MeSATP caused only a small and variable inhibition of cAMP accumulation. Ribonuclease protection analysis of turkey tissues showed that this P2Y purinergic receptor is most highly expressed in blood and brain. Taken together, these results indicate that a phospholipase-C-activating P2Y purinergic receptor has been cloned and stably expressed in 1321N1 astrocytoma cells.
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PMID:Expression of a cloned P2Y purinergic receptor that couples to phospholipase C. 805 61

Pretreatment of 1321N1 human astrocytoma cells with serum induces a pronounced increase in subsequent stimulation by forskolin and other agents of intracellular cyclic AMP accumulation, a phenomenon referred to as sensitization (Mol. Pharmacol. 39, 399-406, 1991). Pretreatment of these cells with lysophosphatidic acid induced sensitization to a similar extent as that with serum (approximately fivefold for forskolin stimulation and twofold for isoproterenol and prostaglandin E1 stimulation), with half-maximal effects at approximately 30 nM lysophosphatidic acid. Phosphatidic acid was effective but less potent whereas other lipids were ineffective. Sensitization by serum and by lysophosphatidic acid were almost completely inhibited by pertussis toxin pretreatment and partially inhibited by prolonged phorbol ester exposure to induce protein kinase C down-regulation. Among nine cell lines tested, those that exhibited sensitization with serum showed comparable sensitization with lysophosphatidic acid. The effects of both lysophosphatidic acid and serum were markedly inhibited by treatment with phospholipase B but only minimally altered with phospholipases A2, D, and C. Exposure of cells to phospholipase C alone induced approximately threefold sensitization, but both serum and lysophosphatidic acid were able to induce further three- to fourfold sensitization above that induced by phospholipase C alone. In contrast, the effects of serum and lysophosphatidic acid were not additive with each other. Together these results suggest that lysophosphatidic acid or a closely related compound present in serum is the factor responsible for sensitization of the cyclic AMP pathway.
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PMID:Lysophosphatidic acid mimics serum-induced sensitization of cyclic AMP accumulation. 822 10

Endothelins (ET-1, -2, -3) display pleiotropic activities, by signalling through G-protein-coupled membrane receptors. We show here that ET-1 and ET-3 stimulate within minutes the tyrosine phosphorylation of a 42 kDa protein (p42) in primary cultures of mouse embryo astrocytes, but not in any of two subclones of rat astrocytoma C6 cells. This effect, measured by anti-phosphotyrosine immunoblotting of cell extracts, was also observed in response to bradykinin, platelet-derived growth factor, the phorbol ester phorbol 12-myristate 13-acetate and the G-protein activator fluoroaluminate. Pretreatment of cells with pertussis toxin, which inactivates Gi/G(o) proteins, did not affect these responses. However, down-regulation of protein kinase C completely blocked the response to phorbol ester and fluoroaluminate and at least partially impaired the ET-1-stimulated phosphorylation of p42. We have identified p42 as p42mapk, a mitogen-activated protein (MAP) kinase, on the basis of the following data: by sequential immunoblotting with antiphosphotyrosine and anti-MAP kinase antibodies, (i) similar kinetics are observed for p42 phosphorylation and the decrease in p42mapk electrophoretic mobility, likely corresponding to its tyrosine/threonine phosphorylation [de Vries-Smits, Boudewijn, Burgering, Leevers, Marshall and Bos (1992) Nature (London) 357, 602-604]; (ii) p42 and the shifted form of p42mapk co-migrate on SDS/PAGE; (iii) the myelin-basic-protein kinase activity of p42mapk is stimulated by ET-1, in parallel with the tyrosine phosphorylation of p42. In conclusion, these findings strongly suggest that endothelins can stimulate the tyrosine phosphorylation and activation of p42mapk in astrocytes, via pertussis-toxin-insensitive G protein and protein kinase C-dependent and -independent pathways.
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PMID:Endothelins stimulate tyrosine phosphorylation and activity of p42/mitogen-activated protein kinase in astrocytes. 834 18

The G-protein-coupled central cannabinoid receptor (CB1) has been shown to be functionally associated with several biological responses including inhibition of adenylate cyclase, modulation of ion channels and induction of the immediate-early gene Krox-24. Using stably transfected Chinese Hamster Ovary cells expressing human CB1 we show here that cannabinoid treatment induces both phosphorylation and activation of mitogen-activated protein (MAP) kinases, and that these effects are inhibited by SR 141716A, a selective CB1 antagonist. The two p42 and p44 kDa MAP kinases are activated in a time- and dose-dependent manner. The rank order of potency for the activation of MAP kinases with various cannabinoid agonists is CP-55940 > delta 9-tetrahydrocannabinol > WIN 55212.2, in agreement with the pharmacological profile of CB1. The activation of MAP kinases is blocked by pertussis toxin but not by treatment with hydrolysis-resistant cyclic AMP analogues. This suggests that the signal transduction pathway between CB1 and MAP kinases involves a pertussis-toxin-sensitive GTP-binding protein and is independent of cyclic AMP metabolism. This coupling of CB1 subtype and mitogenic signal pathway, also observed in the human astrocytoma cell line U373 MG, may explain the mechanism of action underlying cannabinoid-induced Krox-24 induction.
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PMID:Activation of mitogen-activated protein kinases by stimulation of the central cannabinoid receptor CB1. 852 80

1. The effect of mastoparan on phosphatidylcholine hydrolysis was examined in 1321N1 human astrocytoma cells. Mastoparan (3-30 microM) caused an accumulation of diacylglycerol (DG) and phosphatidic acd (PA) accompanied by choline release in a concentration- and time-dependent manner. 2. In the presence of 2% n-butanol, mastoparan (3-100 microM) induced phosphatidylbutanol (PBut) accumulation in a concentration- and time-dependent manner, suggesting that mastoparan activates phospholipase D (PLD). Propranolol (30-300 microM), a phosphatidate phosphohydrolase inhibitor, inhibited DG accumulation induced by mastoparan, supporting this idea. 3. Depletion of extracellular free calcium ion did not alter the effect of mastoparan on PLD activity. 4. A protein kinase C (PKC) inhibitor, calphostin C (1 microM), did not inhibit mastoparan-induce PLD activation but the ability of mastoparan to stimulate phospholipase D activity was decreased in the PKC down regulated cells. 5. PLD activity stimulated by mastoparan was not prevented by pretreatment of the cells with pertussis toxin (PT) or C3 ADP-ribosyltransferase. Furthermore, guanine nucleotides did not affect PLD activity stimulation by mastoparan in membrane preparations. 6. Mastoparan stimulated PLD in several cell lines such as RBL-2H3, RBL-1, HL-60, P388, endothelial cells, as well as 1321N1 human astrocytoma cells. 7. These results suggest that mastoparan induces phosphatidylcholine (PC) hydrolysis by activation of PLD, not by activation of phosphatidylcholine-specific phospholipase C (PC-PLC); mastoparan-induced PLD activation is not mediated by G proteins.
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PMID:Mastoparan-induced phosphatidylcholine hydrolysis by phospholipase D activation in human astrocytoma cells. 864 Mar 50

Pretreatment of 1321N1 human astrocytoma cells with exogenously added bacterial phospholipase C (PLC) induced an increase in subsequent stimulation of cyclic AMP accumulation by the beta-adrenergic receptor agonist isoproterenol and by the direct adenylyl cyclase activator forskolin, a phenomenon referred to as sensitization. The direct protein kinase C activator phorbol 12-myristate 13-acetate (PMA) induced a similar sensitization. In contrast, in C62B rat glioma cells both PLC and PMA induced a decrease in subsequent cyclic AMP accumulation stimulated by isoproterenol and little or no change in stimulation by forskolin. Although the effects of PMA were completely abolished by pretreating cells overnight with PMA to down-regulate protein kinase C activity, the effects of PLC were inhibited only partially or not inhibited. Pertussis toxin pretreatment did not inhibit the sensitization induced by PLC, whereas sensitization induced by lysophosphatidic acid (previously shown to involve pertussis toxin-sensitive GTP binding proteins) was completely inhibited. Further studies of these phenomena may reveal novel pathways for regulation of the cyclic AMP signalling pathway.
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PMID:Modulation of cyclic AMP accumulation in glial cells by exogenous phospholipase C. 882 10


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