Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In human neutrophils, mastoparan induced rapid F-actin polymerization which was followed by a slow and sustained depolymerization to below the initial F-actin content. Incubation of neutrophils with pertussis toxin inhibited mastoparan-stimulated actin polymerization; however it did not prevent sustained depolymerization of F-actin. Analyses of phospholipids performed in parallel revealed that mastoparan stimulated rapid formation of phosphatidylinositol 3,4,5-trisphosphate (PIP3) and consumption of phosphatidylinositol 4,5-bisphosphate (PIP2). Pertussis toxin treatment blocked mastoparan-induced formation of PIP3. Furthermore, mastoparan stimulated the release of N-acetylglucosaminidase from primary granules. Cytochalasin B enhanced mastoparan-stimulated secretion. Mastoparan triggered superoxide radical production in a cytochalasin B-sensitive manner and induced complement type 3 receptor (CR3) up-regulation.
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PMID:Activation of human neutrophils by mastoparan. Reorganization of the cytoskeleton, formation of phosphatidylinositol 3,4,5-trisphosphate, secretion up-regulation of complement receptor type 3 and superoxide anion production are stimulated by mastoparan. 131 28

Membrane-associated protein kinase C has been proposed to be essential in transmembrane signalling systems activating neutrophils. A main function of the neutrophil is phagocytosis and killing of microorganisms. Nevertheless, previously published reports mainly have described the effect of artificial or soluble stimulators upon neutrophil protein kinase C activity. Therefore, membrane-associated protein kinase C was studied in neutrophils stimulated by Staphylococcus albus. The bacteria were found to induce a striking increase in membrane-associated protein kinase C, an effect which depended upon a previous opsonization of the bacteria. Cytochalasin B, which inhibits phagocytosis, was shown to abrogate S. albus-induced protein kinase C translocation. Chelation of intracellular calcium totally abolished S. albus-induced protein kinase C translocation, a phenomenon that could not exclusively be ascribed to chelation of extracellular calcium. The diacylglycerol kinase inhibitor R59022, which has been reported to increase endogenous diacylglycerol accumulation, nearly doubled the effect of S. albus upon membrane-associated protein kinase C. Pertussis toxin in concentrations which completely inhibited fLMP-induced superoxide generation did not affect S. albus-induced protein kinase C translocation. It is concluded that phagocytosis of S. albus is accompanied by a translocation of protein kinase C to the cell membrane, a phenomenon that relies upon enhanced diacylglycerol production and calcium transients and occurs independently of pertussis toxin-inhibitable G-proteins.
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PMID:Staphylococcus albus-induced protein kinase C translocation in human neutrophils: the effect of opsonization, cytochalasin B, pertussis toxin, intra- and extracellular calcium, and R59022. 132 68

Undifferentiated and differentiated HL-60 leukemic cells possess nucleotide receptors which functionally couple to phospholipase C via pertussis toxin-sensitive guanine nucleotide-binding proteins (G-proteins). We investigated the role of extracellular nucleotides in the regulation of beta-glucuronidase release in HL-60 cells. In dibutyryl cyclic AMP (Bt2cAMP)-differentiated HL-60 cells, the chemotactic peptide, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe), the phosphorothioate analogue of ATP, adenosine 5'-O-[3-thio]triphosphate (ATP[gamma S]), and UTP increased cytosolic Ca2+ from 100 nM up to 1.2 microM with EC50 values of 4 nM, 1 microM and 100 nM, respectively. In these cells, ATP[gamma S] induced exocytosis with an EC50 of 4 microM and an effectiveness amounting to 50-70% of that of fMet-Leu-Phe. ATP, ITP, UTP, CTP, and uridine 5'-O-[2-thio]diphosphate activated exocytosis as well. Phorbol myristate acetate (PMA) induced exocytosis with an EC50 of 115 ng/ml and an effectiveness similar to that of ATP[gamma S]. Cytochalasin B (CB) differently potentiated exocytosis induced by ATP[gamma S], fMet-Leu-Phe and PMA. Treatment of Bt2cAMP-differentiated HL-60 cells with pertussis toxin (500 ng/ml) for 24 h resulted in ADP-ribosylation of more than 97.5% of the G-proteins. Under these conditions, pertussis toxin almost completely inhibited the increase in cytosolic Ca2+ and beta-glucuronidase release induced by fMet-Leu-Phe but only partially inhibited the effects of ATP[gamma S] and UTP. fMet-Leu-Phe at a non-stimulatory concentration (1 nM) potentiated ATP[gamma S]-induced beta-glucuronidase release in the presence but not in the absence of CB. In contrast, ATP[gamma S] and fMet-Leu-Phe synergistically activated superoxide formation in the absence of CB. PMA potentiated superoxide formation induced by ATP[gamma S] or fMet-Leu-Phe and did not affect exocytosis induced by ATP[gamma S] or fMet-Leu-Phe. In undifferentiated HL-60 cells, fMet-Leu-Phe, ATP[gamma S], UTP and PMA did not induce beta-glucuronidase release. fMet-Leu-Phe did not increase cytosolic Ca2+ in undifferentiated HL-60 cells, whereas ATP[gamma S] and UTP were similarly potent and effective as in Bt2cAMP-differentiated cells. In differentiated HL-60 cells, fMet-Leu-Phe induced aggregation, and ATP[gamma S] induced a transient shape change. Our results show (I) that exocytosis in HL-60 cells does not obligatorily depend on CB. (II) Purine and pyrimidine nucleotides activate exocytosis via pertussis toxin-sensitive and -insensitive signal transduction pathways.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Nucleotide-, chemotactic peptide- and phorbol ester-induced exocytosis in HL-60 leukemic cells. 196 23

We have investigated the mechanisms of transmembrane signalling implicated in the activation of the respiratory burst of adherent neutrophils by tumor necrosis factor-alpha/cachectin (TNF). The activation of the respiratory burst by TNF is insensitive to pertussis toxin and weakly sensitive to protein kinase C inhibitors. Cytochalasin B and dibutyryl cyclic AMP have an inhibitory effect. The activation of the respiratory burst by TNF takes place in the absence of formation of 3H-inositol phosphates, 32P-phosphatidic acid, and 3H-arachidonic acid. These results demonstrate that the activation of the respiratory burst by an endogenous, physiologic stimulus can be independent of the formation of messengers derived from hydrolysis of phosphoinositides.
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PMID:Tumor necrosis factor-alpha/cachectin activates the O2(-)-generating system of human neutrophils independently of the hydrolysis of phosphoinositides and the release of arachidonic acid. 215 2

Cytochalasins induce little cytochrome c reduction in intact polymorphonuclear leukocytes (PMNs). A strong activation of the respiratory burst is induced by cytochalasin B or by the other cytochalasins, when the dye nitro blue tetrazolium (NBT) is used to measure the burst. Cytochalasin B-induced NBT reduction is dependent on calcium, which is mainly derived from intracellular stores. In the presence of NBT an enhanced binding of [3H]cytochalasin B can be observed. The enhanced reduction of NBT by cytochalasin B-treated cells is completely inhibited by pretreatment of the PMNs with pertussis toxin, suggesting the involvement of a pertussis toxin-sensitive G-protein in cytochalasin-induced activation of the respiratory burst.
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PMID:Cytochalasin-induced nitroblue tetrazolium dye (NBT) reduction in polymorphonuclear leukocytes. 216 72

The neuropeptide substance P (SP), which has been suggested to mediate neurogenic inflammation, induces in human neutrophils the activation of the respiratory burst measured as O2 consumption and H2O2 production, and a cytochalasin B-dependent secretion of specific and azurophilic granules. The SP(4-11) fragment is much more stimulant than the entire molecule, whereas the SP(1-4) fragment is inactive. The respiratory and secretory response to SP are associated with an activation of phosphoinositide turnover, of Ca2+ influx and release from intracellular stores. Pertussis toxin inhibits 70% of the respiratory response and the residual 30% activity remains, even increasing 10-fold the concentration of the toxin. 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine, a putative inhibitor of protein kinase C, does not modify the respiratory response to SP. Cytochalasin B significantly depresses the activation of the respiration by SP, whereas it moderately enhances the activation of phosphoinositide turnover and potentiates the increase of intracellular Ca2+ concentration. The results are discussed in relation to the receptor apparatus involved in SP activity, the signal transduction sequence activated by SP for the stimulation of NADPH oxidase, and the role of cell response to SP in the inflammatory process.
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PMID:Activation of human neutrophils by substance P. Effect on oxidative metabolism, exocytosis, cytosolic Ca2+ concentration and inositol phosphate formation. 245

Diacylglycerol has gained wide acceptance as an important second messenger in the signal transduction mechanism by which occupancy of certain membrane receptors such as the formyl peptide receptor of neutrophils leads to biological responses, but supporting evidence for this proposed role is limited. We have utilized a recently developed diacylglycerol kinase assay (Preiss, J. E., Loomis, C. R., Bishop, W. R., Stein, R., Niedel, J. E., and Bell, R. M. (1986) J. Biol. Chem. 261, 8597-8600) to characterize the diacylglycerol response of normal human neutrophils stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) and other formyl peptides. fMLP alone stimulated a slow, prolonged 36% rise in diacylglycerol levels above basal levels. Cytochalasin B enhances several fMLP-stimulated neutrophil responses, including aggregation, superoxide production, and degranulation. Pretreatment of neutrophils with cytochalasin B markedly increased the rate and extent of the diacylglycerol response to fMLP stimulation. Diacylglycerol peaked at 5 min at 206 +/- 21% above basal levels with a t1/2 of 45 s. The diacylglycerol response was time- and fMLP and cytochalasin B concentration-dependent, appropriate for the known biological activities of several peptide analogues, and completely inhibited by pretreatment with pertussis toxin. These data demonstrate that diacylglycerol may function as a second messenger for neutrophil activation and suggest that cytochalasin B enhancement of neutrophil biology may be the result of an enhanced diacylglycerol response.
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PMID:Cytochalasin B enhancement of the diacylglycerol response in formyl peptide-stimulated neutrophils. 378 96

The cytoskeletal localization of inhibitory guanine-nucleotide-binding (Gi) proteins and the coupling of these proteins to formyl peptide receptors were studied in myeloid differentiated human leukemia (HL-60) cells. Treatment of HL-60 cells with cytochalasin B or botulinum C2 toxin, which leads to the disruption of microfilaments, increased the binding of the stable GTP analogue guanosine 5'[gamma-thio]triphosphate (GTPS[S]) to permeabilized cells by about 30%. In contrast, the microtubule-disrupting agents colchicine and vinblastine, and cytochalasin B treatment of isolated HL-60 membranes did not affect GTP[S] binding. The stimulatory effect of cytochalasin B treatment was concentration and time dependent, with maximal increases observed at 5 micrograms/ml cytochalasin B and an incubation time of 10 min, and was counteracted by the F-actin-stabilizing toxin phalloidin. Cytochalasin B treatment increased the amount of G proteins activated by chemoattractant receptors by about 25%. Furthermore, the number of Gi-protein-coupled receptors for the chemoattractant, N-formyl-Met-Leu-Phe, was increased by about 25% upon cytochalasin B treatment. Based on these functional data, which suggest an association of G proteins with actin filaments, the Triton X-100 (1%)-insoluble cytoskeleton was analyzed for the presence of G proteins. Gia subunits were detected in the cytoskeleton preparations, both by specific antisera and by pertussis-toxin -catalyzed ADP-ribosylation. Cytochalasin B pretreatment depleted the cytoskeleton in Gialpha, with an approximately 20% concomitant increase in membrane Gialpha content. In conclusion, evidence is presented that part of the cellular Gia is localized at actin filaments in HL-60 cells. After filament disruption, these Gia subunits seem to be translocated to the plasma membrance, where they can productively interact with chemoattractant receptors.
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PMID:Translocation of microfilament-associated inhibitory guanine-nucleotide-binding proteins to the plasma membrane in myeloid differentiated human leukemia (HL-60) cells. 865 16

Regulation of renal apical Na+/H+ exchanger 3 (NHE3) activity by adenosine has been suggested to contribute to acute control of mammalian Na(+) homeostasis. The mechanism by which adenosine controls NHE3 activity in a renal cell line was examined. The adenosine analog, N(6)-cyclopentyladenosine (CPA) exerts a bimodal effect on NHE3: CPA concentrations >10(-8) M inactivate NHE3, whereas concentrations <10(-8) M stimulate NHE3 activity. Acute CPA-induced control of NHE3 was blocked by antagonists of A1 adenosine receptors and inhibition of phospholipase C, pretreatment with BAPTA-AM (chelator of cellular calcium), and exposure to pertussis toxin. Stimulatory and to some extent also inhibitory CPA concentrations attenuated 8-bromo-cAMP and dopamine-mediated inhibition of NHE3. BAPTA eliminated the ability of a stimulatory dose of CPA to attenuate 8-bromo-cAMP-induced suppression of NHE3 activity. Upon inhibition of protein kinase C, CPA at an inhibitory dose provoked activation of NHE3, which is partially reverted by 8-bromo-cAMP and suppressed by pre-incubation with BAPTA-AM. Cytochalasin B, an actin-modifying agent, selectively prevented downregulation but did not affect upregulation of NHE3 activity by CPA. In conclusion, these observations demonstrate that (1) CPA modulates NHE3 activity by elevation of cellular Ca(2+) exerting a negative control on adenylate cyclase activity, (2) protein kinase C is the determining factor leading to CPA-induced downregulation of NHE3 activity, and (3) alterations of surface NHE3 abundance may contribute to A1 adenosine receptor-dependent inhibition of NHE3 activity.
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PMID:Bimodal acute effects of A1 adenosine receptor activation on Na+/H+ exchanger 3 in opossum kidney cells. 1281 31