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)

Female Hartley guinea-pigs were immunized with N-phthaloylated ox insulin (96% NA1,NB1,NB29-triphthaloyl ox insulin) using H. pertussis as adjuvant. Haptenic antibody, which was found in antisera taken 20 days after secondary immunization, was assessed for cross-reaction with a series of N-acylated ox insulins. Cross-reaction readily occurred between haptenic antibody and the partial hapten-bearing antigens, NA1-monophthaloyl and NB1-monophthaloyl ox insulins. The immunochemical data suggested that the NA1-glycyl hapten and the NB1-phenylalanyl hapten were both acting as immune determinants for B-lymphocytes, and the determinant competition was taking place between contralateral facets of the principal immunogen, NA1,NB1,NB29-triphthaloyl ox insulin. The data was also consistent with the view that the overall tertiary structure of N-acylated insulins may be very similar to that of their native insulin, the addition of hapten groups having produced only localized areas of structural perturbation.
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PMID:Haptenic antibody induced by N-phthaloylated ox insulin in the Hartley guinea-pig. 7 50

The effect of the neuropeptides substance P, neurokinin A and alpha-calcitonin gene-related peptide (CGRP) on human neutrophil granulocytes was investigated. Substance P induced secondary granule secretion at a concentration of 100 microM. CGRP induced a significant secretory response at 10 microM and thus appeared to be about 10 times more potent than substance P. Calcitonin and a fragment of CGRP, CGRP(8-37), had no effect on neutrophil degranulation. The chemotactic peptide antagonist BOC-MLP (100 microM) inhibited lactoferrin secretion mediated both by CGRP and chemotactic peptide FMLP almost completely, while secretion in response to tumour necrosis factor (TNF) was unaffected. Results from receptor binding studies showed that CGRP and N-formyl-methionyl-leucyl-phenylalanine (FMLP) do not compete for binding. This indicates that CGRP does not exert its effects by binding to the chemotactic peptide receptor. CGRP induced a rapid increase in the cytosolic-free calcium concentration and this increase was not, unlike that induced by FMLP, abolished by preincubation of the cells with pertussis toxin (1000 ng/ml). Therefore CGRP signal transduction in neutrophils appears to involve rapid changes in the cytosolic-free calcium concentration but not a pertussis toxin-sensitive G-protein. In summary, this is the first report to show that CGRP can directly activate neutrophil granulocytes, and this probably occurs via a cell surface receptor which is distinct from that of FMLP although both the CGRP and FMLP-mediated effects can be blocked by BOC-MLP.
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PMID:Calcitonin gene-related peptide (CGRP) activates human neutrophils--inhibition by chemotactic peptide antagonist BOC-MLP. 128 94

Primary cultures of cells from late pregnant rat myometrium contain B2 kinin receptors through which bradykinin (BK) stimulates inositol phosphate (InsP) formation and arachidonic acid (20:4) release. Equilibrium binding at 4 degrees C revealed that [3H]BK identified a maximal number of cell surface B2 kinin receptor binding sites on rat myometrial cells of 308 +/- 78 fmol/10(6) cells with apparently a single equilibrium dissociation constant of 1.8 +/- 0.2 nM. At 37 degrees C, [3H]BK binding was associated with a time-dependent decrease in the reversibility of the binding. This decrease was due in part to formation of slowly dissociating cell surface receptor [3H]BK binding and in part to internalization of the receptor-bound [3H]BK. Exposure of labeled cells to BK resulted in dose-dependent increases in [3H]InsP3, [3H]InsP2 ([3H]Ins(1,4)P2), and [3H]InsP1 ([3H]Ins(1)P1) formation and [3H]20:4 release. Pretreatment with 100 ng/mL pertussis toxin did not perturb BK stimulation of [3H]InsP formation but partially (approximately 30%) inhibited BK stimulation of [3H]20:4 release. BK stimulation of [3H]20:4 release was directly proportional to the number of receptor sites occupied by BK. In contrast, stimulation of [3H]InsP formation required a threshold level of receptor occupancy, which decreased as a function of time of BK exposure. These results show that BK interacts with B2 kinin receptors on rat myometrial cells with apparently a single affinity through which BK stimulates [3H]InsP formation and [3H]20:4 release. BK stimulation of [3H]InsP formation requires a threshold BK concentration, which decreases with time, and we suggest that the decrease is due to a time-dependent formation of a BK receptor binding state from which BK slowly dissociates.
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PMID:Bradykinin binding to B2 kinin receptors and stimulation of phosphoinositide turnover and arachidonic acid release in primary cultures of cells from late pregnant rat myometrium. 133 13

This review outlines evidence that IL-1, IL-2, and TNFs modulate neutrophil functions. These cytokines affect some or all of the following functions of the neutrophil: adherence, cell migration, respiratory burst, lysosomal enzyme release, and cell surface receptor expression. TNFs, especially TNF alpha, remains one of the most highly studied cytokine with respect to regulation of neutrophil function. TNFs are a direct stimuli for the neutrophil respiratory burst and weak stimuli of lysosomal enzyme release. The cytokines enhance cell adhesion and inhibit neutrophil migration. The TNFs augment the oxidative burst and lysosomal enzyme release response to a wide range of soluble and particulate cell stimuli. These changes in the cell seem to be closely correlated with the increased fungicidal, bactericidal, tumoricidal, and protozoacidal activity of the TNF-primed neutrophils. In contrast to TNFs, IL-1 and IL-2 inhibit neutrophil adherence, and this provides evidence that the cytokine family represents a regulatory system. Another form of regulation of TNF alpha and IL-1 neutrophil-activating activity is by the release of inhibitors to these cytokines (58). We have evidence which shows that the soluble TNF alpha inhibitor (a cleaved product of the TNF alpha receptor) (59) binds and inhibits TNF from activating and priming neutrophils (60). Priming of neutrophils by TNFs involves surface receptor binding but is independent of protein kinase C system, pertussis toxin-sensitive guanine nucleotide regulatory protein, and direct burst of respiratory activity. The translocation of cell surface receptors and constituents of the NADPH oxidase from stored vesicles may be the major mechanism of TNF-induced cell priming.
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PMID:Activation of neutrophils by interleukins-1 and -2 and tumor necrosis factors. 150 43

The Shiga toxin family, a group of cytotoxins associated with diarrhoeal diseases and the haemolytic uraemic syndrome, includes Shiga toxin from Shigella dysenteriae type 1 and verotoxins produced by enteropathogenic Escherichia coli. The family belongs to the A-B class of bacterial toxins, which includes the cholera toxin family, pertussis and diphtheria toxins. These toxins all have bipartite structures consisting of an enzymatic A subunit associated with a B oligomer which binds to specific cell-surface receptors, but their amino-acid sequences and pathogenic mechanisms differ. We have determined the crystal structure of the B oligomer of verotoxin-1 from E. coli. The structure unexpectedly resembles that of the B oligomer of the cholera toxin-like heat-labile enterotoxin from E. coli, despite the absence of detectable sequence similarity between these two proteins. This result implies a distant evolutionary relationship between the Shiga toxin and cholera toxin families. We suggest that the cell surface receptor-binding site lies in a cleft between adjacent subunits of the B pentamer, providing a potential target for drugs and vaccines to prevent toxin binding and effect.
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PMID:Crystal structure of the cell-binding B oligomer of verotoxin-1 from E. coli. 174 Oct 63

Cellular receptors for many hormones, neurotransmitters, and growth factors are coupled to intracellular effector enzymes or ion channels through a set of heterotrimeric G proteins. In order to determine whether isoforms of G protein alpha subunits contribute differentially to mitogenic responses, we introduced an alpha subunit isoform, alpha i-1, into Balb/c 3T3 cells that normally lack this subtype. Balb/c 3T3 cells transfected with a plasmid containing cDNA encoding alpha i-1 expressed the alpha i-1 protein as judged both by the appearance of immunoreactive alpha i-1 protein on Western blots and by two-dimensional analysis of the proteins [32P]ADP-ribosylated by pertussis toxin. The amount of alpha i-1 expressed is less than the amount of alpha subunits endogenously present in these cells. Expression of alpha i-1 in the transfected cells slightly blunts stimulation of adenylylcyclase by GTP, guanosine 5'-3-O-(thio)triphosphate, or forskolin, but has no major effect on the ability of thrombin to inhibit the enzyme. In contrast, the expression of alpha i-1 has significant effects on cell growth and on the mitogenic response to thrombin. The alpha i-1-transfected cells have a doubling time that is twice as long as control cells transfected with the same plasmid without a cDNA insert. Despite their slower growth, thymidine incorporation in response to thrombin is greater in transfected than in control cells. Thrombin-stimulated DNA synthesis is sensitive to inhibition by pertussis toxin and is 5-fold more sensitive to inhibition by pertussis toxin in transfected cells than in control cells. The changes are receptor-specific since the mitogenic response to platelet-derived growth factor is indistinguishable between control and transfected cells. These studies suggest that the alpha i subunit composition of the cell may have profound effects on its growth and its response to stimulation through a specific cell surface receptor.
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PMID:Expression of a G protein subunit, alpha i-1, in Balb/c 3T3 cells leads to agonist-specific changes in growth regulation. 193 86

We have used isolated canine parietal cells to examine the receptor and postreceptor events mediating the inhibitory effects of somatostatin on acid secretion. Somatostatin-14 (S14) and somatostatin-28 (S28) dose dependently inhibited parietal cells stimulated by secretagogues that activate both the adenylate cyclase/cyclic adenosine monophosphate and the inositol phospholipid/protein kinase C cascades. The inhibitory action was mediated via a specific cell surface receptor that consists of a single subunit protein (molecular weight 99,000 d). This receptor recognized S14 and S28 equally well. Somatostatin inhibited parietal cell activity via mechanisms that are both dependent on and independent of a pertussis toxin-sensitive inhibitory guanine nucleotide binding protein.
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PMID:Cellular mechanisms of somatostatin action in the gut. 197 8

Pertussis toxin activates T lymphocytes by a mechanism that is independent of its ADP-ribosylation activity. The toxin stimulates increases in diacylglycerol and intracellular calcium apparently by interacting with a cell surface receptor. Consistent with the production of these second messengers we have found that pertussis toxin activates protein kinase C in the Jurkat cell line. The toxin was also found to activate a tyrosine protein kinase in these cells in a manner similar to that observed with phytohemagglutinin. These results provide evidence that the mechanism of activation of T cells by pertussis toxin involves stimulating the activity of protein kinase C and a tyrosine protein kinase.
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PMID:Pertussis toxin activates protein kinase C and a tyrosine protein kinase in the human T cell line Jurkat. 246 93

The binding of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine to its cell surface receptor rapidly elicits the hydrolysis of phosphatidylinositol 4,5-bisphosphate by phospholipase C to form the putative second messengers inositol 1,4,5-trisphosphate and sn-1,2-diacylglycerol. To investigate the possible role of a guanine nucleotide binding protein in transduction of this membrane signal, we examined the effects of pertussis toxin on chemotactic peptide-stimulated inositol phospholipid metabolism in differentiated HL-60 cells labeled with [3H]inositol. Pertussis toxin inhibited the chemotactic tripeptide-stimulated production of inositol mono-, bis-, and trisphosphates and secretion of N-acetyl-beta-D-glucosaminidase in a time- and concentration-dependent manner. Treatment with pertussis toxin did not alter the total incorporation or the distribution of [3H]inositol in inositol phospholipid. Chemotactic peptide receptor number was unchanged, although a slight decrease in binding affinity was observed. These findings suggest a role for a guanine nucleotide binding protein in coupling the chemotactic peptide receptor to phospholipase C.
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PMID:Pertussis toxin inhibits chemotactic peptide-stimulated generation of inositol phosphates and lysosomal enzyme secretion in human leukemic (HL-60) cells. 286 Jun 68

Pertussis toxin (PT) catalyzes the ADP-ribosylation of several guanine nucleotide-binding (G) proteins that are involved in the transduction of cell surface receptor-mediated signals. Involvement of such G-proteins in regulation of hematopoiesis by two growth factors, colony-stimulating factor-1 (CSF-1) and interleukin 3 (IL 3), was investigated using pertussis toxin. Continuous or pulse exposure of murine bone marrow cells to pertussis toxin inhibited CSF-1 or IL 3-induced colony formation by approximately 50%. Pertussis toxin inhibition was also demonstrated against partially separated marrow from 5-fluorouracil-treated mice. The toxin effect was blocked by heating (95 degrees C for 30 minutes), by antitoxin antibody and was not associated with increased cAMP levels in target cells. In experiments with murine marrow, toxin-mediated inhibition appeared to involve predominantly the macrophage lineage. IL 3 stimulation of proliferation of the murine marrow-derived factor-dependent cell line FDC-P1, as measured by 3H-TdR incorporation, and CSF-1 stimulation of pure populations of murine bone marrow derived macrophages, as measured by DNA content and cell number, was also inhibited. Analysis of the effects of pertussis toxin on the growth of single cells stimulated by IL 3 demonstrated that this inhibition involved a decreased growth rate rather than a toxic ablation of cells. Phorbol myristate acetate (PMA) stimulated FDC-P1 cells and was able to abrogate the PT inhibition of IL 3 stimulation of these cells, suggesting but not establishing that IL 3 may mediate its proliferative effects through activating protein kinase C.
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PMID:Inhibition of interleukin 3 and colony-stimulating factor 1-stimulated marrow cell proliferation by pertussis toxin. 312 45


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