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 synthesis of the neuropeptide precursor proenkephalin was measured in bovine adrenal chromaffin cells following radiolabeling with [35S]methionine. Treatment of chromaffin cells with pertussis toxin (100 ng/ml) approximately doubled proenkephalin synthesis without altering total protein synthesis. Pertussis toxin pretreatment also increased proenkephalin synthesis in chromaffin cells exposed to vasoactive intestinal peptide (VIP) and 3-isobutyl-1-methylxanthine (IBMX). Combinations of IBMX plus nicotine, VIP, or histamine also synergistically enhanced proenkephalin synthesis, with no further elevation when the cells were also pretreated with pertussis toxin. The action of forskolin, a direct activator of adenylate cyclase, on proenkephalin synthesis was similarly potentiated by pertussis toxin or IBMX, presumably reflecting the abilities of both the toxin and this phosphodiesterase inhibitor to enhance the cyclic AMP response to forskolin. In contrast, increased synthesis of proenkephalin in response to phorbol esters was not affected by pertussis toxin treatment. These results suggest that pertussis toxin potentiates proenkephalin synthesis primarily through inactivation of guanine nucleotide-binding proteins that inhibit adenylate cyclase, although other signaling pathways may also be involved.
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PMID:Pertussis toxin enhances proenkephalin synthesis in bovine chromaffin cells. 769 72

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

Oxidized low-density lipoprotein (LDL) inhibits signalling pathways mediated by pertussis toxin-sensitive guanine nucleotide-binding proteins (Gi proteins). To determine whether this inhibition is due to altered G protein alpha i subunit expression, mRNA and protein levels of alpha i isoforms were assessed in bovine aortic endothelial cells treated with oxidized LDL (0-100 micrograms/ml, 0-72 h). Oxidized LDL did not affect the expression of alpha i3, but did cause time- and concentration-dependent decrease in alpha i2 mRNA and protein resulting in a 3.2- and 3.5-fold reduction, respectively, after 72 h. This decrease in alpha i2 coincided with a 86% decrease in alpha i2 GTPase activity. Nuclear run-off studies did not show any significant effect of oxidized LDL on alpha i2 or alpha i3 transcription. In the presence of actinomycin D, oxidized LDL shortened the t1/2 of alpha i2 mRNA from 16 h to 8 h which was attenuated by cycloheximide. In addition, pulse-chase labelling with [35S]methionine revealed that oxidized LDL reduced the t1/2 of alpha i2 protein from 27 to 14 h. Our results indicate that oxidized LDL can modulate receptor-Gi coupling by downregulating the expression of alpha i2, but not alpha i3. The mechanism involves both mRNA destabilization and protein degradation.
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PMID:Regulation of G-protein alpha i2 subunit expression by oxidized low-density lipoprotein. 770 49

A primary cellular site involved in heat shock response of eukaryotic cells is located in plasma membranes. The mechanism by which heat shock is sensed and the signals that trigger heat shock response remain an enigma. We aim to determine the role of guanine-nucleotide binding proteins (G)-proteins in mediating heat shock response in eukaryotic cells. The effect of heat shock on high affinity GTPase activity in presence or absence of modulators of G-proteins, such as pertussis toxin was studied by measuring GTPase catalyzed release of 32[Pi] from gamma-32[P]GTP. The effect of pertussis toxin on induction of heat shock proteins in cells subjected to thermal stress was studied by SDS-PAGE analysis of 35[S]-methionine labelled cellular proteins. Exposure of cultured human malignant cells to thermal stress (43 degrees C) resulted in a significant increase in activity of high affinity GTPase in the membranes (P < 0.001). This response to heat shock was inhibited by prior exposure of the cells to nanogram concentrations of pertussis toxin, suggesting the involvement of G-proteins in mediating heat shock response. To characterize this G-protein dependence further, we assayed thermal stress stimulated high affinity GTPase activity in cells pretreated with antisera (AS/7) raised against a synthetic peptide corresponding to the last 10 amino acids of alpha-subunit of inhibitory G-protein (Gi). A partial reduction in heat shock induced stimulation of GTPase activity was observed in the presence of this antisera. The pertussis toxin treated cells did not show induction of heat shock proteins in response to thermal stress.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heat stress stimulates high affinity GTPase in cervical carcinoma cells. 778 Aug 30

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


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