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)

Digital fluorescence calcium imaging was used to investigate and identify the primary biological responses of human neutrophils to monomeric immunoglobulin E (IgE). Treatment of neutrophils with IgE caused a transient rise in the level of intracellular calcium that was inhibited by pertussis toxin. The calcium rise was due mainly to release from an intracellular membrane-enclosed store that is also sensitive to the chemotactic peptide formyl-Met-Leu-Phe. The IgE-induced calcium transient was independent of Fc gamma receptors and of Fc epsilon receptor ligation. Our data suggest that the mere binding of IgE to neutrophils is sufficient to evoke a biological response without the need for IgE/receptor cross-linking.
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PMID:Monomeric human IgE evokes a transient calcium rise in individual human neutrophils. 756 23

Upon binding to their receptors on the surface of neutrophils, chemotactic peptides elicit a burst of metabolic activity. The excess acid generated by this burst must be rapidly extruded in order to maintain intracellular pH and preserve normal microbicidal responses. Recently, H(+)-pumping vacuolar-type ATPases (V-pumps) and a H(+)-selective conductance were described in the membrane of neutrophils. However, these systems are virtually quiescent in resting cells. In this report, we analyzed whether the V-pumps and the conductance become active and contribute to pH regulation following cell activation by chemoattractants. Formyl-Met-Leu-Phe (fMLP) was found to stimulate V-pumps, as assessed by the appearance of bafilomycin-sensitive H+ extrusion. Concomitantly, the chemoattractant also activated the H+ conductance, detected as a voltage-dependent and Zn(2+)-sensitive net H+ efflux. In both cases, activation was prevented by treatment with competing antagonistic peptides or with pertussis toxin, implying mediation by a receptor coupled to a heterotrimeric G protein. The signalling pathways downstream of the G proteins were also investigated. Stimulation of neither the V-pump nor the conductance required activation of protein kinase C. An elevation of cytosolic calcium ([Ca2+]i) comparable to that induced by fMLP did not suffice to trigger either transporter. Moreover activation of the conductance remained unaffected when the chemoattractant-induced increase in [Ca2+]i was precluded. In contrast, stimulation of the V-pump was substantially (approximately 50%) depressed when [Ca2+]i was prevented from rising. Tyrosine phosphorylation of several polypeptides accompanies stimulation by fMLP. Prevention of phosphotyrosine accumulation resulted in a pronounced inhibition of H(+)-pumping and of the H+ conductance. Together, these data indicate that engagement of surface receptors by chemotactic peptides can lead to stimulation of two voltage-sensitive pH regulatory pathways, a pump and a conductance, by a pathway that requires tyrosine phosphorylation. Both pathways are capable of sizable H+ extrusion, thereby contributing to pH regulation during the metabolic burst.
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PMID:Chemoattractant-induced activation of vacuolar H+ pumps and of an H(+)-selective conductance in neutrophils. 759 38

We have shown previously that guinea pig alveolar macrophages (AM) synthesize a secretory phospholipase A2 (PLA2) during in vitro incubation. Here, we report the molecular cloning of this enzyme and show that it has structural features closely related to all known mammalian type-II PLA2. The mRNA and PLA2 activity were undetectable in freshly collected AM, but their levels increased dramatically to reach maximal values after 16 h of culture. Thereafter, the PLA2 activity remained constant with a parallel secretion in the medium, in contrast to mRNA level which returned to near basal values after 32 h. Incubation of AM for 16 h with the inflammatory secretagogue peptide f-Met-Leu-Phe (fMLP) markedly reduced the PLA2 activity and mRNA levels. This inhibition was prevented by preexposure of AM to pertussis toxin, an inhibitor of G-protein. In contrast, when AM were first cultured for 16 h and then incubated with fMLP, no significant change was observed in their PLA2 activity. In conditions where the type-II PLA2 was completely abrogated by fMLP, the latter did not alter the lipopolysaccharide-induced accumulation of tumor necrosis factor alpha mRNA or the release of arachidonic acid induced by the subsequent addition of the calcium ionophore A23187. These studies show that the inflammatory peptide fMLP down-regulates the expression of the type-II PLA2 by AM through a process mediated by G-protein. A possible negative control of the type-II PLA2 expression during AM activation is suggested.
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PMID:Expression of the type-II phospholipase A2 in alveolar macrophages. Down-regulation by an inflammatory signal. 761 34

Because of the high intracellular Cl- concentration ([Cl-]i) in gastrointestinal smooth muscle, receptor-mediated opening of Cl- channels at the cell resting potential could represent a plausible mechanism for initial receptor-mediated cell depolarization. To test this hypothesis, we characterized activation of large-conductance Cl- channels by the neurokinin-1 (NK-1) receptor agonist [Sar9,Met(O2)11]-substance P, by specific second messengers, and by direct G protein activation in myocytes isolated from the rabbit colon longitudinal muscle layer. In excised inside-out patches, large-conductance ion channels selective for Cl- over Na+ could be induced by holding the patch at pipette potentials values > 60 mV. The channel showed multiple smaller conductance states (< or = 20) but could open and close via a main gate. When the channel was fully open, its slope conductance was 300 pS, with substates as small as 15 pS, comparable to the predominant conductance observed in cell-attached patches. The voltage-activation profile for full conductance was bell-shaped with maximal open probability (Po) for channel opening of approximately 0 mV. In cell-attached patches, addition of the NK-1 agonist to pipette solution activated a channel that corresponded to a subconductance state of the maxi Cl- channel. The voltage-activation profile for this subconductance state showed a maximal Po value for membrane potentials of approximately 0 mV, with rapid inactivation at more positive and partial inactivation at more negative membrane potentials. In excised inside-out patches, both the full and smaller conductance states of the Cl- channel were activated by the nonhydrolyzable guanosine triphosphate analogue guanosine 5'-O-(3-thiotriphosphate) and inhibited by pertussis toxin (PTX), whereas [Ca2+]i increased channel activity only in concentrations > 1 mM. In cell-attached patches, addition of different Ca2+ ionophores resulted in channel activation in 10% of cells, and activators of protein kinase A or protein kinase C had no effect. These findings are consistent with the hypothesis of a possible role of G protein-coupled Cl- channels in receptor-mediated initial cell depolarization in longitudinal colonic smooth muscle.
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PMID:Chloride channels in myocytes from rabbit colon are regulated by a pertussis toxin-sensitive G protein. 768 83

The influence of childhood pertussis infection and of purified pertussis toxin on histamine release from human basophil leucocytes was investigated. Three different stimuli, the peptide N-formyl-Met-Phe (NFMP), anti-IgE, and the calciumionophore A23187 were used to challenge the cells. When NFMP was the stimulus, histamine release in the control group (age 0.5-17 years) increased in an age-dependent fashion, whereas anti-IgE and A23187 stimulated release did not vary with age. During the convulsive state of pertussis infection there was a significant reduction of histamine release in response to 10 microM NFMP (from 9.5 +/- 1.4 [n = 21] to 6.7 +/- 1.5 [n = 19], P < 0.05) and in response to 800 and 80 U/ml anti-IgE (from 28.5 +/- 5 [n = 19] to 16.3 +/- 5 [n = 13], P < 0.05, and from 6.9 +/- 1.7 [n = 16] to 2 +/- 0.8 [n = 13], P < 0.01), whereas histamine release stimulated by A23187 was unchanged compared to release in control children. In vitro pretreatment of basophils from healthy children and adults with pertussis toxin also inhibited histamine release. When NFMP was the stimulus, release was completely blocked by pertussis toxin with an IC50 of about 11 ng/ml, whereas anti-IgE stimulated release was only inhibited by 20%-30% and release induced by A23187 was reduced to 40%-50% by toxin treatment. In conclusion we have demonstrated a functional impairment of histamine release during the convulsive state of pertussis and that this inhibition is likely to be mediated by pertussis toxin.
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PMID:Histamine release from basophils in childhood: age dependency and inhibition by pertussis infection and pertussis toxin. 768 56

The activation of the respiratory burst by complement factor 5a (C5a), platelet-activating factor (PAF), formyl-Met-Leu-Phe (fMLP) and neutrophil-activating peptide IL-8 was explored in eosinophils from patients with the hypereosinophilic syndrome. The amplitude of the response increased with increasing concentrations of C5a and PAF, but the time for its induction was unaffected by the amount of stimulus applied. Respiratory burst activity resulting from phorbol 12-myristate, 13-acetate (PMA)-mediated activation of protein kinase C (PKC) produced longer onset times, which shortened with increasing PMA concentrations. Total inhibition of the C5a- and PMA-mediated burst could be achieved with the PKC inhibitor staurosporine at concentrations of 100 and 5nM, respectively. Calcium depletion abolished agonist-induced rises in cytosolic free calcium ([Ca2+]i) and respiratory burst activity, but not PMA-mediated NADPH-oxidase activation. While PMA reduced elevations in [Ca2+]i, it restored the burst response to agonists in Ca(2+)-depleted eosinophils. These results agree with the agonist-induced activation of the NADPH-oxidase via PKC, but suggest a parallel, Ca(2+)-, phospholipase C- and PKC-independent signal transduction pathway. Data obtained with B. pertussis toxin showed that the respiratory burst in eosinophils is blocked by ADP-ribosylation of G(i)-proteins, but that in the presence of PMA portions of the agonist response could be recovered.
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PMID:Activation of the respiratory burst in eosinophil leucocytes--a transduction sequence decoupled from cytosolic Ca2+ rise. 770 83

Previous studies have demonstrated that the alpha 2A-adrenergic receptor (alpha 2A AR) incorporates [3H]palmitate and that replacement of Cys442 by Ala or Ser eliminates detectable acylation without perturbing coupling to pertussis toxin-sensitive GTP-binding proteins (Kennedy, M. E., and Limbird, L. E. (1993) J. Biol. Chem. 268, 8003-8011) or, as shown here, without perturbing agonist-dependent receptor phosphorylation, in contrast to the consequences of eliminating beta 2-adrenergic receptor acylation. As a first step in revealing the functional role for this post-translational modification at the alpha 2A AR, we explored sequences in the alpha 2AAR which confer alpha 2AAR acylation and whether or not [3H]palmitoylation of the alpha 2AAR is dynamic. Deletion of the 7 terminal amino acids distal to Cys442 of the alpha 2AAR did not eliminate detectable [3H]palmitoylation of the alpha 2AAR, whereas truncation to Leu441 did, indicating both that Cys442 is the likely site for acylation and that sequences distal to Cys442 are not required for acylation at Cys442. Since mutation of sequences proximal to Cys442 altered overall receptor structure, based on markedly reduced detectable adrenergic receptor binding, proximal motifs required for palmitoylation of the alpha 2AAR could not be explored further. When the turnover of [35S]Met/Cys-labeled alpha 2AAR was compared with the turnover of the [3H]palmitate-labeled alpha 2AAR, it was of interest that agonist treatment accelerated the half-life of decay of the [3H]palmitate-labeled alpha 2AAR without detectable receptor down-regulation, providing evidence that the acylation of the alpha 2AAR may be a dynamic process.
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PMID:Palmitoylation of the alpha 2A-adrenergic receptor. Analysis of the sequence requirements for and the dynamic properties of alpha 2A-adrenergic receptor palmitoylation. 798 67

The neuronal growth-associated protein GAP-43 is expressed maximally during development and regeneration, and is enriched at the cytosolic surface of the growth cone membrane. GAP-43 can activate the GTP-binding protein G(o) which is also a major component of the growth cone membrane. These findings have led to the hypothesis that GAP-43 might modulate neurite outgrowth by altering G-protein activity. Here we define the sequence requirements for GAP-43 amino terminal peptide stimulation of G(o), and test these peptides as potential modulators of neurite outgrowth. The first 10 amino acids of GAP-43, Met-Leu-Cys-Cys-Met-Arg-Arg-Thr-Lys-Gln, stimulate G(o). Substitutions at particular residues reveal that cys3, cys4, arg6, and lys9 are critical, but arg7 is not. Both the GAP-43(1-10) peptide and the G-protein-activating peptide mastoparan induce growth cone collapse and inhibit neurite extension from embryonic chick dorsal root ganglion and retinal neurons. This is likely to be mediated by G-proteins: pertussis toxin blocks the inhibition, and mutant peptides that do not activate G(o) do not alter outgrowth. In contrast to the case with embryonic chick dorsal root ganglion cells, neurite outgrowth from N1E-115 neuroblastoma cells is stimulated by GAP-43(1-10). This is probably also a G-protein-mediated event because it is blocked by pertussis toxin, because the sequence requirements match those for G(o) stimulation, and because mastoparan stimulates outgrowth from these cells. The longer GAP-43(1-25) peptide does not alter neurite outgrowth unless the cells are permeabilized, suggesting an intracellular site of action. These data identify a novel set of compounds that modulate neurite outgrowth, and also support the notion that GAP-43 can alter neurite extension by modulating pertussis toxin-sensitive G-protein activity in the growth cone.
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PMID:GAP-43 amino terminal peptides modulate growth cone morphology and neurite outgrowth. 808 50

1. The electrophysiological action of the mu-opioid receptor-preferring agonist D-Ala2, MePhe4, Met(O)5-ol-enkephalin (FK 33-824) on synaptic transmission has been studied in area CA3 of organotypic rat hippocampal slice cultures. 2. FK 33-824 (1 microM) had no effect on the amplitude of pharmacologically isolated N-methyl-D-aspartate (NMDA) or non-NMDA receptor-mediated EPSPs. 3. FK 33-824 (10 nM to 10 microM) reduced the amplitude of monosynaptic inhibitory postsynaptic potentials (IPSPs) that were elicited in pyramidal cells with local stimulation after pharmacological blockade of excitatory amino acid receptors. This effect was reversible, dose-dependent, and sensitive to naloxone and the mu-receptor antagonist Cys2,Tyr3,Orn5,Pen7-amide (CTOP). FK 33-824 at 1 microM caused a mean reduction in the amplitude of the monosynaptic IPSP of 70%. 4. Neither delta- nor kappa-receptor-preferring agonists had any effect on excitatory or inhibitory synaptic potentials. 5. The disinhibitory action of FK 33-824 was blocked by incubating the cultures with pertussis toxin (500 ng/ml for 48 h) or by stimulation of protein kinase C with phorbol 12,13-dibutyrate (PDBu, 0.5 microM). 6. The depression of monosynaptic IPSPs by FK 33-824 was unaffected by extracellular application of the K+ channel blockers Ba2+ or Cs+ (1 mM each). 7. FK 33-824 produced a decrease in the frequency of miniature, action potential-independent, spontaneous inhibitory synaptic currents (mIPSCs) recorded with whole-cell voltage-clamp techniques, but did not change their mean amplitude. Application of the Ca2+ channel blocker Cd2+ (100 microM) or of nominally Ca(2+)-free solutions did not alter either the frequency and amplitude of mIPSCs or the reduction of mIPSC frequency induced by FK 33-824. 8. The effect of FK 33-824 on spontaneous mIPSCs was prevented by naloxone, and by incubation of cultures with pertussis toxin. 9. These results indicate that mu-opioid receptors decrease GABA release presynaptically by a G protein-mediated inhibition of the vesicular GABA release process, and not by changes in axon terminal K+ or Ca2+ conductances that are sensitive to extracellular Ba2+, Cs+ or Cd2+.
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PMID:Mechanism of mu-opioid receptor-mediated presynaptic inhibition in the rat hippocampus in vitro. 830 42

N-Formyl-Met-Leu-Phe (FMLP), at concentrations as low as 5 nM, caused an increase in intracellular uridine pools in dimethyl sulphoxide (Me2SO)-differentiated HL-60 cells. Intracellular uridine pools were elevated rapidly and reached a maximum within 10 min of exposure to 10 microM FMLP, followed by a gradual decline. This enhancement by FMLP was a consequence of a 3-fold increase in the Vmax of pertussis-toxin-sensitive Na(+)-dependent uridine transport system, with no change in the apparent Km. Km values of 2.67 +/- 0.45 and 3.85 +/- 0.52 microM and Vmax. values of 0.046 +/- 0.017 and 0.125 +/- 0.020 microM/s were obtained for untreated and FMLP-treated Me2SO-differentiated cells respectively. The effect of FMLP on the Na(+)-dependent transport of uridine in Me2SO-differentiated HL-60 cells was specific, as the facilitated transport of uridine was unaffected. Furthermore, this phenomenon was not observed in undifferentiated, phorbol 12-myristate 13-acetate (PMA)-differentiated or pertussis-toxin-treated Me2SO-differentiated HL-60 cells. Removal of extracellular Ca2+ with EGTA abolished the FMLP enhancement of uridine transport in a reversible manner, suggesting the involvement of Ca2+. However, the Ca2+ ionophore A23187 only partially mimicked the effect of FMLP. Similarly, with PMA the transport was sub-optimally enhanced, but a full activation was observed in cells treated with both A23187 and PMA. These findings suggest that activation of the Na(+)-dependent uridine transporter by FMLP in Me2SO-differentiated HL-60 cells involves a pertussis-toxin-sensitive G-protein with a bifurcating signal-transduction pathway.
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PMID:Enhancement of pertussis-toxin-sensitive Na(+)-dependent uridine transporter activity in HL-60 granulocytes by N-formylmethionyl-leucyl-phenylalanine. 837 25


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