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)

Triethyl lead chloride (Et3PbCl) was found to induce a shift of fatty acids from membrane phospholipids to triacylglycerols in the human promyelocytic leukemia cell line HL-60. High concentrations of Et3PbCl (greater than 10 microM) caused a substantial liberation of [14C]arachidonic acid within 10 to 20 min in dimethyl sulfoxide-differentiated cells, comparable to the effect of the calcium ionophore A23187 (10 microM). Following liberation of arachidonic acid, its metabolites could be detected. Prolongation of the incubation time and reduction of Et3PbCl concentration resulted in a shift of fatty acids from phospholipids to triacylglycerols. Deacylation of phospholipids and reacylation into phospholipids and triacylglycerols were in equilibrium when the cells were treated with Et3PbCl at concentrations of less than or equal to 10 microM for 5 hr or less than or equal to 1 microM for 24 hr; no increase of free fatty acids could be observed, and the loss of fatty acids within the phospholipids was equivalent to the increase of fatty acid content within the triacylglycerols. Moreover, under these conditions, no loss of viability was seen after 24 hr, as compared with untreated differentiated cells. This concentration- and time-dependent effect of Et3PbCl might be due to a stimulated liberation of fatty acids via phospholipase A2, because this stimulation could be totally prevented by the phospholipase inhibitors quinacrine and p-bromophenacylbromide. Additionally, pretreatment of differentiated HL-60 cells with pertussis toxin resulted in a drastic reduction of [14C]arachidonic acid liberation when cells were stimulated with Et3PbCl. These results suggest the involvement of a pertussis toxin-sensitive GTP-binding protein and of a signal transduction mechanism during stimulated fatty acid release; release does not seem to be via a direct stimulation of phospholipase activity by the lead compound.
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PMID:Directed shift of fatty acids from phospholipids to triacylglycerols in HL-60 cells induced by nanomolar concentrations of triethyl lead chloride: involvement of a pertussis toxin-sensitive pathway. 190 39

Neuropeptide Y (NPY) is a unique peptide with wide distribution in central and peripheral nervous systems. In the guinea pig, NPY-positive fibers are prominent in the myenteric plexus. To test whether NPY inhibits myenteric plexus acetylcholine (ACh) release and to define mechanisms, a purified preparation of myenteric plexus neurons was derived from the teniae coli of neonatal guinea pigs and maintained in primary culture. Incubation of cultured neurons labeled with [3H]ACh in the presence of NPY (10(-14)-10(-6) M) significantly inhibited basal ACh release (83 +/- 16 to 58 +/- 11% of control). NPY significantly inhibited ACh release stimulated by potassium (55 mM); by adenylate cyclase agonists forskolin (10(-6) M) and cholera toxin (10(-8) M); and by calcitonin gene-related peptide, cholecystokinin octapeptide, and vasoactive intestinal peptide (each 10(-8) M). In each instance, the inhibitory effects of NPY were reversed by preincubation with pertussis toxin. Reversal of inhibitory effects by pertussis toxin suggests that the actions of NPY are mediated via an inhibitory GTP-binding protein.
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PMID:Inhibition of acetylcholine release from guinea pig myenteric neurons by neuropeptide Y: GTP-binding protein mediation. 190 63

Activation of the membrane-associated NADPH oxidase in intact human neutrophils requires a receptor-associated heterotrimeric GTP-binding protein that is sensitive to pertussis toxin. Activation of this NADPH oxidase by arachidonate in a cell-free system requires an additional downstream pertussis toxin-insensitive G protein (Gabig, T. G., English, D., Akard, L. P., and Schell, M. J. (1987) (J. Biol. Chem. 262, 1685-1690) that is located in the cytosolic fraction of unstimulated cells (Gabig, T. G., Eklund, E. A., Potter, G. B., and Dykes, J. R. (1990) J. Immunol. 145, 945-951). In the present study, immunodepletion of G proteins from the cytosolic fraction of unstimulated neutrophils resulted in a loss of the ability to activate NADPH oxidase in the membrane fraction. The activity in immunodepleted cytosol was fully reconstituted by a partially purified fraction from neutrophil cytosol that contained a 21-kDa GTP-binding protein. Purified human recombinant Krev-1 p21 also completely reconstituted immunodepleted cytosol whereas recombinant human H-ras p21 or yeast RAS GTP-binding proteins had no reconstitutive activity. Rabbit antisera raised against a synthetic peptide corresponding to the effector region of Krev-1 (amino acids 31-43) completely inhibited cell-free NADPH oxidase activation, and this inhibition was blocked by the synthetic 31-43 peptide. An inhibitory monoclonal antibody specific for ras p21 amino acids 60-77 (Y13-259) had no effect on cell-free NADPH oxidase activation. Activation of the NADPH oxidase in intact neutrophils by stimulation with phorbol myristate acetate caused a marked increase in the amount of membrane-associated antigen recognized by 151 antiserum on Western blot. Thus a G protein in the cytosol of unstimulated neutrophils antigenically and functionally related to Krev-1 may be the downstream effector G protein for NADPH oxidase activation. This system represents a unique model to study molecular interactions of a ras-like G protein.
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PMID:Resolution of a low molecular weight G protein in neutrophil cytosol required for NADPH oxidase activation and reconstitution by recombinant Krev-1 protein. 190 90

We have characterized a soluble pertussis toxin (PT)-sensitive GTP-binding protein (G-protein) present in mouse mastocytoma P-815 cells. 65% of total ADP-ribosylation of PT substrate having a molecular mass of 40 kDa on SDS-polyacrylamide gel electrophoresis in cell homogenate was detected in the supernatant after centrifugation at 100,000 x g for 90 min. [32P]ADP-ribosylation of cytosolic PT substrate was significantly enhanced on the addition of exogenous beta gamma complex. The molecular mass of the cytosolic PT substrate was estimated to be about 80 kDa on an Ultrogel AcA 44 column, but the beta gamma complex was not detected in the cytosol by using the anti-beta gamma complex antibody. Furthermore, the cytosolic PT substrate was found to have some unique properties: [35S]GTP gamma S binding was not inhibited by GDP and [32P]ADP-ribosylation was not affected by GTP gamma S treatment. Only after the cytosolic PT substrate had been mixed with exogenous beta gamma complex, did it copurify with exogenous beta gamma complex by several column chromatographies including an Octyl-Sepharose CL-4B column. The PT substrate was identified as Gi2 alpha by Western blot analysis and peptide mapping with S. aureus V8 protease. These results suggest that Gi2 alpha without beta gamma complex exists with an apparent molecular mass of about 80 kDa in the cytosolic fraction of P-815 cells.
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PMID:Characterization of cytosolic pertussis toxin-sensitive GTP-binding protein in mastocytoma P-815 cells. 190 93

The mechanisms responsible for initiating the conversion of globular to filamentous actin (assembly) after stimulation of B lymphocytes and the role of these cytoskeletal changes in cell activation are incompletely understood. We investigated the molecular basis of the signals leading to actin polymerization and concentrated on the involvement of guanosine triphosphate (GTP)-binding regulatory proteins, and protein kinase C (PKC). In addition, we related these early events to later events in B-cell activation, including cell proliferation. Cross-linking the Ag receptor with Staphylococcus aureus Cowan I (SAC) or anti-IgM antibodies, or stimulation of PKC with phorbol ester induced a time- and concentration-dependent increase in the filamentous actin content of B cells. Inhibition or depletion of PKC resulted in decreased actin assembly induced by anti-IgM, SAC, and PMA, suggesting that the signal for polymerization is generated distally to PKC activation. Pertussis toxin pretreatment inhibited the responses to anti-IgM and SAC but not PMA, and direct stimulation of permeabilized cells with GTP gamma S induced microfilament assembly, indicating the involvement of a GTP-binding protein for receptor-mediated events. Disruption of actin polymerization with botulinum C2 toxin or cytochalasin D inhibited the assembly of actin and [3H]TdR incorporation induced by all stimuli. We conclude that human B cell activation by receptor-mediated stimuli results in actin polymerization by signaling pathways coupled to GTP-binding proteins. These changes in the cytoskeleton may be involved in the transduction of messages leading to responses such as proliferation in B lymphocytes.
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PMID:Microfilament assembly is required for antigen-receptor-mediated activation of human B lymphocytes. 190 89

A high density of nerve fibers containing calcitonin-gene-related peptide (CGRP) is present in the atria. Recently CGRP was reported to open ATP-sensitive K channels in arterial smooth muscle cells. This study examines whether CGRP activates a similar K+ channel in cardiac cells. In voltage-clamped whole cells loaded with GTP and ATP, CGRP reversibly evoked an inwardly rectifying K+ current. To identify the K+ channel that gives rise to this current, three types of K+ channel (resting, ATP-sensitive and acetylcholine-activated) were examined. CGRP failed to activate or inhibit the ATP-sensitive or the resting K+ channel. However, CGRP (0.1-1 microM) caused activation of single channels with kinetics similar to that of the muscarinic K+ channel (35-40 pS conductance and approx. 1 ms mean open time in symmetrical 140 mM K+). In excised, inside-out (CGRP in pipette) or in outside-out (GTP in pipette) patches, the K+ current was activated by perfusion with GTP or CGRP, respectively, suggesting that CGRP activated the muscarinic K+ channel via GTP-binding protein. Treatment with pertussis toxin inhibited the activation of the K+ channel, suggesting that CGRP receptor may be coupled to a Gi or a Go type of GTP-binding protein. Together with previous findings, these results suggest that CGRP modulates several types of ion channels to produce its cellular effects.
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PMID:Calcitonin-gene-related peptide activates the muscarinic-gated K+ current in atrial cells. 190 72

Pretreatment of partially purified inhibitory GTP-binding protein (Gi, 41 kDa) with activated cyclic AMP-dependent protein kinase (PKA) decreases its ADP-ribosylation by islet-activating protein (pertussis toxin, IAP). We examined whether this decrease was associated with dissociation of the trimer of alpha beta gamma-subunits of Gi protein into alpha-subunits and beta gamma-subunits. Results showed that phosphorylation of the Gi protein by PKA impaired its dissociation into alpha-subunits and beta gamma-subunits by 50 mM Mg2+ and 100 microM GTP gamma S. The results suggested that phosphorylation of the Gi protein by PKA possibly caused a conformational change of the trimer Gi protein.
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PMID:Phosphorylation of Gi protein by cyclic AMP-dependent protein kinase inhibits its dissociation into alpha-subunits and beta gamma-subunits by Mg2+ and GTP gamma S. 190 64

To examine whether GTP-binding protein(s) is (are) involved in adipocyte differentiation, the effect of pertussis toxin (PT) was studied in rat adipocyte precursor cell culture. PT potentiated adipose conversion induced by dexamethasone, insulin, and 1-methyl-3-isobutylxanthine in a dose- and time-dependent fashion. Attenuation of an inhibitory control of adenylate cyclase was not the mechanism of action of PT. The dose-dependent inhibition of PT-catalyzed ADP-ribosylation of the Mr 40,000 protein of the cell membrane by preincubation of the toxin was inversely related to the potentiating effect on differentiation. PT-sensitive G protein(s) may be involved in adipocyte differentiation in a negative fashion.
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PMID:Enhancement of differentiation of rat adipocyte precursor cells by pertussis toxin. 193 Nov 59

The characteristics of the activation of a histone H4 kinase activity in Triton X-100 lysates of rabbit peritoneal neutrophils pretreated with fMet-Leu-Phe were studied: The activation of the kinase was a) inhibited by the antagonist of formylpeptide, t-Boc-(Phe-Leu)2(-)-Phe, b) completely inhibited by pertussis toxin pretreatment, c) not affected by the pretreatment of neutrophils with an activator of protein kinase C, phorbol-12-myristate-13-acetate, or an inhibitor of protein kinase C, 1-(5-isoquinoline-sulfonyl)-2-methyl-piperazine, and d) not inhibited in the cells preloaded with the intracellular calcium chelators, bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetra acetic acid acetoxymethyl-ester (BAPTA/AM). These results suggest that the stimulus-induced activation of H4 kinase requires functional receptor and GTP-binding protein but neither calcium mobilization nor protein kinase C activation.
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PMID:Stimulation of a histone H4 protein kinase in Triton X-100 lysates of rabbit peritoneal neutrophils pretreated with chemotactic factors: lack of requirements of calcium mobilization and protein kinase C activation. 196 52

The effect of the vasodilatory peptide bradykinin on the regulation of phosphoinositide metabolism in endothelial cells was investigated. Activation of phosphoinositide metabolism by bradykinin in the endothelium of the bovine pulmonary artery was not blocked by pertussis toxin, which ADP-ribosylates a membrane protein of molecular mass 40 kDa, but botulinum toxin, which ADP-ribosylates a membrane protein of molecular mass 24 kDa, fully blocked bradykinin-stimulated phosphoinositide metabolism. The effect of bradykinin was potentiated by guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S), an activator of GTP-binding proteins, and inhibited by guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S), an inhibitor of GTP-binding proteins. Activation of phosphoinositide metabolism by bradykinin was fully blocked by a B2-receptor antagonist, whereas a B1-receptor antagonist did not affect bradykinin action. It is concluded that the B2-receptor in endothelial cells is coupled to phospholipase C via a GTP-binding protein, which is a substrate for botulinum toxin.
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PMID:Regulation by bradykinin of phosphoinositide metabolism in the endothelial cells of the pulmonary artery. 196 71


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