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)

Hormone-induced Ca2+ mobilization in rat parotid acinar cells is reportedly mediated via an as yet uncharacterized G protein. We have studied the sensitivity to pertussis toxin (PTx) of this signal transduction mechanism. When rats were treated with Ptx (1.3-1.5 micrograms per animal) for 72 h, a 41 kDa membrane protein was ADP-ribosylated. This PTx treatment regimen, also, resulted in a more than 80% block of the ability of the muscarinic agonist carbachol to inhibit beta-adrenergic receptor-stimulated parotid adenylyl cyclase activity. However, cytosolic Ca2+ levels, in response to either carbachol or AIF-4, were comparable in cells prepared from both untreated or PTx-treated rats, when incubated either in the absence or presence of extracellular Ca2+. Further, both the sensitivity of the Ca2+ response to carbachol and the ability of the agonist-sensitive intracellular Ca2+ stores to be refilled by extracellular Ca2+ were unaffected by PTx treatment. Parotid membranes also contained three low-molecular-weight GTP-binding proteins (25, 22 and 18 kDa) which were unaffected by PTx. These results show that there is only one detectable substrate in parotid membranes for a PTx-catalyzed ADP-ribosylation and that hormone-induced Ca2+ mobilization events in parotid acinar cells are not mediated via PTx-sensitive components.
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PMID:Evidence against a role for a pertussis toxin-sensitive G protein in Ca2+ mobilization in rat parotid acinar cells. 212 29

Streptolysin O-permeabilized cells incubated with a high concentration (5-10 mg/ml) of cytosolic proteins and ATP-generating system exhibit redistribution into the endoplasmic reticulum (ER) of Golgi integral proteins (mannosidase II, galactosyltransferase, TGN 38), detected by immunofluorescence. In addition, mannosidase II is detected in the ER of cells exposed to a high concentration of cytosolic proteins and processed for immunolectron microscopy by immunoperoxidase. The redistribution process requires ATP and is not affected by previous microtubule depolymerization. Ultrastructural observations indicate that Golgi disassembly occurs by budding of coated vesicles. This stage of the process is inhibited by GTP-gamma S, AIF(3-5), transducin beta gamma subunits, and mastoparan, indicating the involvement of trimeric G proteins. At a later stage, vesicles lose their coats and fuse with the ER. This part of the process does not occur in cells incubated at either 15 degrees C or 20 degrees C, or exposed to N-ethylmaleimide. In cells treated with either cholera or pertussis toxin Golgi redistribution into the ER shows a 50-fold lower requirement for cytosolic factors than in untreated cells. These data suggest a regulatory role for both alpha s and alpha i trimeric G proteins in the normal Golgi-ER retrograde transport taking place in intact cells.
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PMID:Trimeric G proteins regulate the cytosol-induced redistribution of Golgi enzymes into the endoplasmic reticulum. 761 93

The regulatory mechanism(s) of a phosphoinositide-specific phospholipase C, PLC-delta 1, was investigated using a clone of stably overexpressed PLC-delta 1 (PLC delta 30 cells) in Chinese hamster ovary cells. Thrombin stimulation of PLC delta 30 cells exhibited 6.5-fold increase in total inositol phosphates (InsP), which was significantly higher than that in the vector-transfected (V1) cells (2.0-fold). AIF-4 increased InsP accumulation in both V1 and PLC delta 30 cells, and pertussis toxin partially blocked InsP accumulation in thrombin-stimulated PLC delta 30 cells. Guanosine thiotriphosphate (GTP gamma S) markedly potentiated thrombin-stimulated InsP generation in permeabilized PLC delta 30 cells compared with V1 cells, suggesting possible involvement of a G-protein (s) in the activation of PLC-delta 1. In PLC delta 30 cells, ionomycin-induced significant InsP generation and thrombin-stimulated InsP generation were completely inhibited by addition of EGTA. Furthermore, the stimulatory effects of thrombin plus GTP gamma S in PLC delta 30 cells were more sensitive to change in free calcium concentration than in V1 cells. Suppression by 12-O-tetradecanoylphorbol 13-acetate of thrombin-stimulated InsP accumulation was not affected by increasing Ca2+ concentration. These results indicate that thrombin-induced PLC-delta 1 activation is regulated via both G-protein(s) and calcium.
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PMID:Thrombin-mediated phosphoinositide hydrolysis in Chinese hamster ovary cells overexpressing phospholipase C-delta 1. 819 39

Previously, we have shown that both T and B lymphocytes from chronically nicotine-treated (NT) animals exhibit tolerance to activation by Ags (ligation of Ag receptors), as indicated by their decreased ability to mobilize intracellular calcium and, at least in T cells, arrest of cells in the G0/G1 phase of the cell cycle. Herein, we demonstrate that NT T cells significantly lose their ability to up-regulate inositol trisphosphate synthesis in response to TCR ligation or nonspecific activation of G proteins by AIF-4. However, increases in cAMP concentrations of T cells following activation of G protein-sensitive adenylate cyclase by cholera or pertussis toxin were not significantly affected by the nicotine treatment. Interestingly, compared with control T cells, the background levels of inositol trisphosphate were significantly elevated in NT T cells, indicating some degree of activation in these cells. This inference was further supported by observations that naive T cells from NT animals exhibit tyrosine phosphorylation of several substrates, including phospholipase C-gamma1, which were either absent or underphosphorylated in unstimulated control T cells. Moreover, when, after 4-wk nicotine treatment, nicotine pumps were removed and serum cotinine levels fell to background, inhibition of the Ab-forming cells and Ca2+ responses continued for at least 2 more wk. These results suggest that chronic in vivo nicotine exposure leads to T cell anergy and may contribute to nicotine/cigarette smoke-induced immunosuppression.
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PMID:Effects of nicotine on the immune response. II. Chronic nicotine treatment induces T cell anergy. 878 95

Theileria parva sporozoites rapidly enter bovine lymphocytes. Since lymphocytes are normally nonphagocytes sporozoite binding to the host cell surface must initiate events in the host cell, leading to the internalization of the parasite. In the present study inhibitors of various key molecules in cell signal transduction and activation pathways, in combination with a method of quantitation, have been used to examine the possible role(s) of these systems in sporozoite entry. A variety of protein kinase inhibitors caused significant inhibition of sporozoite entry. Moreover, protein kinase activities in both the sporozoite and the host cell were essential to sporozoite invasion. Down-regulation of lymphocyte protein kinase C and inhibitors of phospholipase C but not phospholipase A2 activity also blocked sporozoite entry. Parasite entry could also be blocked by inhibitors of G protein activity. Treatment of sporozoites with AIF(3-5) blocked parasite binding while treatment of host cells inhibited sporozoite internalization. Furthermore, sporozoite entry was dependent on a cholera toxin-inhibitable process(es), whereas mastroparan and pertussis toxin had no significant inhibitory effects. Collectively these results provide initial evidence for both parasite protein kinase- and G protein-dependent processes as well as the participation of a variety of host cell signal transduction pathways in the sporozoite entry process.
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PMID:Theileria parva sporozoite entry into bovine lymphocytes involves both parasite and host cell signal transduction processes. 894 24

We have demonstrated previously that D1 dopamine receptors are coupled to both Gs alpha and Go alpha. We examine here the coupling between human D5 dopamine receptors and G proteins in transfected rat pituitary GH4C1 cells. Similar to D1 receptors, cholera toxin treatment of cells reduced, but did not abolish, D5 agonist high-affinity binding sites, indicating D5 receptors couple to both Gs alpha and cholera toxin-insensitive G proteins. The interaction between D5 receptors and Gs alpha was confirmed by immunoprecipitation studies and by the ability of D5 receptors to stimulate adenylyl cyclase. Unlike D1 receptors, D5 receptors did not display any pertussis toxin-sensitive G-protein coupling to Go alpha or Gi alpha. D5 receptors were also not coupled to Gq alpha and were unable to mediate phosphatidylinositol metabolism. Instead, D5 sites appeared to be coupled to an AIF(-)4-sensitive, N-ethylmaleimide-resistant G protein. Anti-Gz alpha caused immunoprecipitation of 24.2 +/- 5.2% of G protein-associated D5 receptors, indicating coupling between D5 and Gz alpha. The coupling to Gz alpha was specific for D5 receptors, because similar associations were not detected between D1 receptors and Gz alpha.
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PMID:Multiple coupling of human D5 dopamine receptors to guanine nucleotide binding proteins Gs and Gz. 960 10

Phagocytosis is a receptor-mediated process by which specialized cell types engulf large extracellular particles. Phagosome maturation involves a series of intracellular membrane fusion and budding events resulting in the delivery of particles to compartments enriched in lysosomal hydrolases where they are digested. Substantial amounts of plasma membrane and many phagosomal proteins, such as receptors, rapidly recycle to the plasma membrane following phagosome formation. Despite the importance of this recycling pathway in phagosome maturation and in the retrieval of immunogenic peptides from phagosomes, the molecular machinery involved is largely unknown. To assess the participation of GTPases in phagocytosis and recycling from phagosomes we used aluminum fluoride (AIF(-)(4)), which activates the GDP-bound form of stimulatory and inhibitory trimeric G proteins. AlF(-)(4) inhibited both the uptake to and the recycling from the phagosomal compartment. Cholera toxin, which activates Galphas, and pertussis toxin, which uncouples Gi and Go from receptors, were effective inhibitors of phagocytosis. However, both toxins stimulated recycling from phagosomes. These results suggest that more than one GTP-binding protein participates either directly or indirectly not only in phagocytosis, but also in maturation and recycling from phagosomes, and thereby assign a role for heterotrimeric G proteins in controlling traffic through the phagocytic pathway.
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PMID:Involvement of heterotrimeric G proteins in phagocytosis and recycling from the phagosomal compartment. 1169 95