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)

The effects of 4-beta phorbol 12-myristate 13-acetate (PMA) on hormone and forskolin-stimulated adenylate cyclase were evaluated in S49 lymphoma cells. Treatment of wild type (WT) S49 cells with PMA caused stimulation, inhibition or had no effect on epinephrine stimulation of cAMP accumulation. The effect observed was dependent on the length of PMA treatment, the concentration of PMA and the concentration of hormone (or forskolin) used to stimulate cAMP accumulation. Longer treatment times with PMA and higher PMA concentrations favored the inhibitory effects. Pretreating WT with 0.5 microM PMA for 18 min caused an increase in the EC50 and maximal levels for epinephrine stimulation of cAMP accumulation. Thus inhibition was seen at relatively low epinephrine concentrations and augmentation with high concentrations. The inhibitory effects of PMA on epinephrine-stimulated adenylate cyclase activity were observed only at low free Mg++ concentrations (0.75 mM). The effects of PMA on PGE1-stimulated cAMP accumulation were similar to those observed for epinephrine. In S49 WT cells 100 nM PMA augmented 5 microM forskolin-stimulated cAMP accumulation; however with 100 microM forskolin, PMA effects were minimal. PMA also attenuated Gi-mediated Gpp(NH)p inhibition of forskolin-stimulated adenylate cyclase in both WT and cyc- membranes, resembling the effects of pertussis toxin. The effects of various phorbol analogues on epinephrine-stimulated cAMP accumulation were as follows: 4 beta-phorbol 12,13-didecanoate had similar effects to PMA, 4 alpha-phorbol 12,13-didecanoate had no effects and 1-oleoyl, 2-acetylglycerol augmented epinephrine-stimulated cAMP accumulation at concentrations greater than or equal to 5 microM. Our results are consistent with a dual mechanism of PMA action on adenylate cyclase involving protein kinase C-mediated phosphorylation of Gi and of the beta-adrenergic receptor, the former leading to augmentation and the latter to inhibition of hormone-stimulated adenylate cyclase.
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PMID:Phorbol ester-induced augmentation and inhibition of epinephrine-stimulated adenylate cyclase in S49 lymphoma cells. 302 Jan

Lipopolysaccharide, a component of the outer membrane of Gram-negative bacteria, activates B lymphocytes and macrophages. Pertussis toxin, which inactivates several members of the G protein family of signaling components, including Gi and transducin, was found to inhibit the lipopolysaccharide-induced responses of the WEHI-231 B lymphoma cell line and the P388D1 macrophage cell line. These results, combined with the demonstration that lipopolysaccharide inhibits adenylate cyclase activity in P388D1 cells, strongly argues that lipopolysaccharide activation of cells is mediated by a Gi-like receptor-effector coupling protein.
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PMID:Pertussis toxin inhibition of B cell and macrophage responses to bacterial lipopolysaccharide. 309 21

We reported previously that cold exposure increases by 2- to 3-times the maximal responsiveness of interscapular brown adipose tissue (IBAT) adenylate cyclase to stimulation by norepinephrine or fluoride and that the sensitizing effect of cold is the result of an increase in neural transmission to the tissue because it is abolished by prior surgical denervation of IBAT. The present report examined further the molecular basis of the sensitization of IBAT adenylate cyclase. Cold exposure increased the maximal responsiveness of adenylate cyclase to stimulation by guanylyl-5'-imidodiphosphate without altering the apparent affinity of the enzyme for the nucleotide. In addition, cold exposure increased the maximal extent of cholera toxin-mediated ADP-ribosylation of the alpha subunit of the stimulatory regulatory protein of adenylate cyclase (Gs alpha) in proportion to the increase in adenylate cyclase activity, but did not alter pertussis toxin-mediated labeling of the inhibitory regulatory protein. Direct measurement of Gs alpha by immunoblotting, however, revealed that sensitized membranes did not contain more Gs alpha protein. These results indicate that neural stimulation of IBAT produced by cold exposure alters the proportion of existing Gs molecules that are functional. The additional observation that sensitized adenylate cyclase activity did not reconstitute into cyc- S-49 lymphoma membranes suggests that the ability of neural stimulation to increase Gs function in IBAT might depend upon the interaction of Gs with factors that are unique to membranes of cold-exposed rats.
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PMID:Neural modulation of the stimulatory regulatory protein of adenylate cyclase in rat brown adipose tissue. 313 62

Exposure of lactogen-dependent Nb2 lymphoma cells to prolactin for up to 72 hr caused time- and dose-dependent changes in the ability of specific 38 kDa and 41.5 kDa membrane proteins from these cells to be subsequently ADP-ribosylated by pertussis and cholera toxins, respectively. Whereas the sensitivity of the 41.5 kDa substrate to cholera toxin was already reduced after 1 hour, that of the 38 kDa substrate for cholera toxin was increased for up to 72 hours. These findings suggest that membrane G-proteins may mediate the effects of prolactin binding to its receptor, leading to the proliferation of Nb2 lymphoma cells.
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PMID:Prolactin differentially affects bacterial toxin-induced ADP-ribosylation of Nb2 lymphoma cell membrane proteins. 314 63

Fusion of noninvasive, nonmetastatic BW5147 T-lymphoma cells with normal T-lymphocytes usually resulted in highly invasive and metastatic T-cell hybridomas, apparently due to properties derived from the normal T-cell. Occasionally hybrids arose that were non- or low invasive, probably by loss of relevant genes upon chromosome segregation, since these cells contained much less DNA than highly invasive hybrids. The metastatic potential of 20 representative T-cell hybridomas was tested by tail vein injection in syngeneic mice and cells were found to be either nonmetastatic (NM), low metastatic (LM), or high metastatic (HM). NM hybrids were tumorigenic but did not form metastases and HM hybridomas caused wide-spread metastasis. LM cells formed metastases in a limited number of mice and predominantly in lymphoid tissues. In hepatocyte cultures, NM cell lines were found to be the least invasive, HM cells the most, whereas LM hybrids exhibited intermediate levels. Invasiveness was not only measured in rat hepatocyte cultures but also in rat embryo fibroblast monolayers, and the relative invasive capacity in both model systems correlated well. Pertussis toxin inhibited invasion in both systems to 20-30% of control values. This suggests that the mechanisms of invasion into hepatocyte and fibroblast cultures are at least partially similar and that the fibroblast invasion assay is a relevant model to study aspects of lymphoma metastasis. We conclude that invasive potential is a prerequisite for T-cell hybridomas to colonize tissues from the bloodstream and that a minimum level of invasiveness is necessary for extensive and wide-spread metastasis formation.
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PMID:Invasiveness in hepatocyte and fibroblast monolayers and metastatic potential of T-cell hybridomas in mice. 328 95

Protease digestion of the ADP-ribosylated pertussis toxin substrate (PTS) protein was carried out after solubilization with SDS (Cleveland gels) and in the intact membrane. Cleveland gel analysis showed substantial similarities in the maps for the PTS component in neutrophils, platelets and erythrocytes and also in the S49 AC-lymphoma cell line. In the intact membrane ADP-ribosylation followed by digestion showed limited access of proteases to the PTS component. Of eight proteases tested, only papain and Staphylococcus aureus gave substantial digestion. This pattern was observed in the human platelet, erythrocyte and neutrophil plasma membranes. When the sequence was reversed and ADP-ribosylation was carried out after protease digestion, a very different pattern was observed with much greater susceptibility to digestion being noted with several proteases. By contrast, analysis of the murine AC-membrane showed some minor variations in the digest patterns. In addition, under all three conditions tested, maps of the cholera toxin substrate for the human platelet showed remarkable similarities to those obtained with the pertussis toxin substrate. Our results indicate that the protease sensitive sites of the alpha subunit of PTS and protection from proteolysis after ADP-ribosylation are properties which are shared by the PTS components of human platelets, erythrocytes and neutrophils.
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PMID:Peptide mapping studies of the pertussis toxin substrate in human neutrophils, platelets and erythrocytes. 328 41

We have investigated whether cholera toxin (CT)- or pertussis toxin (IAP)-sensitive G proteins are involved in ovine (o) PRL-stimulated mitogenesis in the lactogen-dependent rat Nb2 node lymphoma cell line. Addition of IAP to medium caused a biphasic effect on oPRL-stimulated cell number. Low doses (10(-3) ng/ml) enhanced (mean +/- SEM, 15 +/- 3%) whereas higher doses (greater than or equal to 10 ng/ml) inhibited (24 +/- 3%) mitogenesis stimulated by a submaximal dose of oPRL (0.1 ng/ml) compared to control values. The cAMP analog 8-bromo-cAMP also had a biphasic effect on cell division stimulated by submaximal doses of PRL. Low doses (10(-5) M) enhanced whereas higher doses (10(-3) M) inhibited Nb2 cell growth in response to PRL. Incubation with CT only inhibited oPRL-stimulated mitogenesis in a dose-dependent manner. Maximal inhibition (63 +/- 7%) occurred at a concentration of 10 ng/ml or more. Phorbol myristate acetate (PMA) enhanced mitogenesis stimulated by PRL alone and in the presence of either stimulatory or inhibitory doses of IAP, but PMA did not block IAP inhibition. In contrast, PMA had no effect on cells incubated with CT; the inhibition of PRL-stimulated cell division by CT remained unchanged. Lactogenic receptor-binding sites per cell and affinity were not significantly affected by PMA, IAP, or CT, suggesting a postreceptor mechanism of action. In summary, these data demonstrate that cAMP modifies PRL-stimulated Nb2 cell mitogenesis. The differences between IAP and CT (i.e. biphasic effect, degree of inhibition, and differential effect of PMA) suggest that these agents could also modulate PRL actions in the Nb2 cell through different mechanisms, including a cAMP-independent pathway.
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PMID:Modulation of prolactin-stimulated Nb2 lymphoma cell mitogenesis by cholera toxin and pertussis toxin. 338 78

We have examined whether pertussis toxin, an agent known to inhibit entry of normal lymphocytes into tissues, affects invasion and metastasis formation by malignant lymphoma and T-cell hybridoma cells. The toxin reduced invasion in vitro in hepatocyte cultures to 20% of control values. Inhibition was maximal after pretreatment for 2 h with approximately 100 ng/ml. The effect of pretreatment with 1 to 5 micrograms toxin/ml for 4 h persisted for at least 5 days, despite a more than 100-fold increase in cell number. The proliferation rate was not affected. Liver metastasis formation after tail vein injection of TAM2D2 T-cell hybridoma cells in syngeneic AKR mice, measured as liver weight, was reduced to 10 to 25% of controls after pretreatment of the cells for 4 h with 1 microgram pertussis toxin/ml. Metastasis to kidneys, ovaries, and lymph nodes was not, or less evidently, affected. With MB6A lymphosarcoma cells no effect was seen after treatment with 1 microgram/ml, but a significant reduction of the liver tumor burden to approximately 50% of controls was achieved by treatment with at least 5 micrograms toxin/ml. Spleen metastasis by MB6A cells was not affected. These results provide evidence for a similarity in invasion mechanisms of normal and malignant lymphoid cells, and they suggest that invasiveness is an important factor in the formation of lymphoma metastases, particularly in the liver.
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PMID:Inhibition of lymphoma invasion and liver metastasis formation by pertussis toxin. 365 46

Adenosine, acting via A1 adenosine receptors, can inhibit adenylate cyclase activity in adipocytes. To assess the effects of chronic adenosine agonist exposure on the A1 adenosine receptor system of adipocytes, rats were infused with (-)-phenylisopropyladenosine or vehicle for 6 days and membranes were prepared. Basal as well as isoproterenol-, sodium fluoride-, and forskolin-stimulated adenylate cyclase activities were significantly increased (approximately 2-fold) in membranes from treated animals. (-)-Phenylisopropyladenosine-mediated inhibition of forskolin-stimulated adenylate cyclase activity was significantly (p = 0.0001) attenuated in membranes from treated rats (20.1 +/- 2.1% inhibition) versus controls (31.6 +/- 2.3% inhibition). Prostaglandin E1-induced inhibition of forskolin-stimulated adenylate cyclase activity was also attenuated: 11.7 +/- 3.6 versus 23.2 +/- 4.6% (p = 0.001). Using the A1 adenosine receptor agonist radioligand (-)-N6-(3-[125I]iodo-4-hydroxyphenylisopropyl)adenosine, 32% fewer high affinity binding sites were detected in membranes from treated animals (p less than 0.04). Photoaffinity labeling with N6-2-(3-[125I]iodo-4-azidophenyl)ethyladenosine revealed no gross difference in receptor structure. The number of beta-adrenergic receptors as well as the percentage of receptors in the high affinity state as assessed by (-)-3-[125I]iodocyanopindolol binding were the same in both groups. In membranes from treated rats, the amount of [alpha-32P]NAD incorporated by pertussis toxin into the alpha subunit of the inhibitory guanine nucleotide regulatory protein (Ni) was decreased by 37 +/- 11%. Concurrently, the quantity of label incorporated by cholera toxin into the alpha subunit of the stimulatory guanine nucleotide regulatory protein (Ns) was increased by 44 +/- 14% in treated membranes. Finally, the capacity of Ns solubilized from treated membranes to stimulate adenylate cyclase activity when reconstituted into cyc- S49 lymphoma cell membranes was enhanced by approximately 50% compared to control. Thus, heterologous desensitization, manifested by a diminished capacity to inhibit adenylate cyclase and an enhanced responsiveness to stimulatory effectors, can be induced in the A1 adenosine receptor-adenylate cyclase system of adipocytes. A decrease in Ni alpha subunit concomitant with an increase in Ns alpha subunit quantity and activity may represent the biochemical mechanism of desensitization in this system.
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PMID:Heterologous desensitization of the inhibitory A1 adenosine receptor-adenylate cyclase system in rat adipocytes. Regulation of both Ns and Ni. 380 10

Rat reticulocytes contain a cytosol activator protein (RCAP) that augments hormone-sensitive adenylate cyclase activity in the rat reticulocyte and other systems. In a previous publication, using a highly purified preparation of RCAP, we reported that the stimulatory guanine nucleotide-binding protein (Ns) was required for the actions of RCAP. We investigated this possibility by studying the actions of RCAP on cholera toxin-dependent ADP ribosylation of Ns. RCAP decreased cholera toxin-dependent ADP ribosylation of the 42,000-dalton subunit of Ns of reticulocyte [40.2 +/- 3.7 (+/-SEM) to 26.5 +/- 3.8 fmol/mg; n = 10; P less than 0.001], S49 wild-type (33.9 +/- 2.4 to 24.9 +/- 2.8 fmol/mg; n = 9; P less than 0.01), and UNC (25.3 +/- 3.5 vs. 17.6 +/- 3.1; n = 5; P less than 0.02) membranes. In contrast, pertussis toxin-dependent ADP-ribosylation of the inhibitory guanine nucleotide binding protein, Ni in reticulocyte, S49 wild-type lymphoma, and its UNC and cyc- variant membranes were all significantly augmented by RCAP. Moreover, when reticulocyte Ni was functionally ablated by exposure to pertussis toxin, RCAP no longer enhanced isoproterenol-responsive adenylate cyclase activity in reticulocyte membranes. These results suggest that RCAP stimulates adenylate cyclase activity by inhibiting Ni function, thus permitting enhanced Ns coupling to the adenylate cyclase enzyme (C).
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PMID:Reticulocyte cytosol activator protein: effects on the stimulatory and inhibitory regulatory proteins of adenylate cyclase. 392 80


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