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)

Administration of diphtheria and tetanus toxoids and pertussis vaccine adsorbed (DTP vaccine) or endotoxin (LPS) resulted in marked alterations in hepatic drug-metabolizing enzymes in endotoxin-responsive (R) and non-endotoxin-responsive (NR) mice. A single human dose (0.5 ml) of DTP vaccine increased hexobarbital-induced sleep times to 1.6- to 1.8-fold above those of controls in both strains of mice. This effect persisted for 7 days. In contrast, Bordetella pertussis LPS-treated mice showed an increase at 1 day (3.0-fold for R mice and 1.5-fold for NR mice), which returned to control levels by day 7. Furthermore, cytochrome P-450 levels were decreased 30 to 40% 24 h after DTP vaccine administration in both R and NR mice, while after LPS administration they were decreased 30% in R mice and less than 10% in NR mice. Both spleen and liver weights of R and NR mice were increased 7 to 14 days following DTP vaccine administration. However, LPS treatment had no apparent effect on liver weights, and spleen weights of R mice were elevated from days 3 to 7. Histopathologic tissue examination showed random, multifocal inflammation with hepatocyte necrosis after DTP vaccine administration to both R and NR mice and an absence of lesions in LPS-treated mice. Premixing LPS with polymyxin eliminated the increased sleep times, but premixing DTP vaccine with polymyxin did not affect the increased sleep times. Levels of tumor necrosis factor and interleukin-6 in plasma of R mice were markedly increased after DTP and LPS treatment, while NR mice had reduced increases. These results suggest that LPS contributes to the alterations in R and NR mice seen within the first 24 h of vaccine administration but that it is not likely to contribute to the effects observed at later time points.
Infect Immun 1992 Sep
PMID:Role of endotoxin in alterations of hepatic drug metabolism by diphtheria and tetanus toxoids and pertussis vaccine adsorbed. 150 Jan 88

To determine the effect of protein isoprenylation with farnesyl vs geranylgeranyl groups on membrane association in vivo, COS cells were transfected with cDNAs encoding the wild-type G-protein alpha i1 (WT) subunit, the soluble nonmyristoylated G-protein alpha i1 glycine to alanine mutant (GA), a double mutant in which the carboxy-terminal residues CGLF of GA were mutated to CVLS (GA-CVLS), and a double mutant in which the carboxy terminus of GA was mutated to CALL (GA-CALL). As opposed to the WT and GA proteins, the GA-CVLS and GA-CALL proteins were not pertussis toxin substrates nor were they recognized by antibodies that recognize the nonmutated alpha i1 carboxy terminus. Only the GA-CVLS and GA-CALL proteins incorporated [3H]mevalonate in the form of a farnesyl and a geranylgeranyl moiety, respectively. Subcellular localization, as assessed by immunoblotting and immunoprecipitation, revealed that the WT protein localizes almost exclusively to the membrane fraction, whereas the GA, GA-CVLS, and GA-CALL proteins localize predominantly to the soluble fraction. The soluble GA-CVLS and GA-CALL proteins were not carboxyl methylated, but the small amount localized to the membrane was partially carboxyl methylated. These results indicate that neither farnesylation nor geranylgeranylation is sufficient alone to lead to membrane association.
Biochemistry 1992 Sep 01
PMID:Differential isoprenylation of carboxy-terminal mutants of an inhibitory G-protein alpha-subunit: neither farnesylation nor geranylgeranylation is sufficient for membrane attachment. 151 Sep 88

Heterotrimeric G proteins are believed to play important roles as signal transducing components in various mammalian sperm functions. To assess the distribution of G proteins in bovine sperm tails, we purified membranes by hypoosmotic swelling of bovine spermatozoa followed by disruption of plasma membranes in a homogenizer and various centrifugation steps. Electron microscopy revealed highly purified membranes of bovine sperm tails. Subsequently, antisera against synthetic peptides were used to identify G proteins in immunoblots. An antiserum directed against the C-terminal decapeptide of Gi3 and detecting all known pertussis toxin-sensitive alpha-subunits, reacted specifically with a 40-kDa protein. In contrast, various other specific peptide antisera against alpha-subunits did not detect any G protein in enriched tail membranes. An antiserum recognizing the beta 2-subunit of G proteins and an antiserum reacting with both beta 1- and beta 2-subunits identified a 35-kDa protein in sperm tail membranes. In contrast, antisera against the 36-kDa beta 1-subunit did not detect any relevant proteins in the membrane fraction. Neither G protein alpha-subunits nor G protein beta-subunits were found in the cytosol. Our results suggest that G proteins in membranes of tails of bovine spermatozoa most likely belong to a novel subtype of G protein alpha-subunits, whereas the putative beta-subunit could be identified as a beta 2-subunit.
Biol Reprod 1992 Sep
PMID:Immunological identification of G protein alpha- and beta-subunits in tail membranes of bovine spermatozoa. 151 Oct 86

Phytohemagglutinin (PHA) injection induces transient protease-sensitive traffic of lymphocytes in skin and other tissues in several species. Examination of the possible roles of cytokines in such reactions showed that recombinant bovine and human tumor necrosis factor (TNF)-alpha potently induce dose-dependent lymphocyte traffic in pig skin (and in other tissues including the draining lymph nodes) with early kinetics and a morphology of the inflammatory reaction similar to that of PHA (peaking 9-12 h). Recombinant human interleukin (IL)-1 alpha also induces dose-dependent lymphocyte traffic, but it peaks at 4 h. Entry of labeled lymphocytes into inflammatory sites induced by PHA, TNF-alpha and IL-1 alpha, but not into normal skin, is inhibited by approximately 80% by their pretreatment with trypsin, indicative of the induction of endothelial determinants recognized by protease-sensitive surface molecules on the lymphocytes. Even the minimal lymphocyte traffic induced by interferon-gamma and lipopolysaccharide was similarly protease sensitive. At the earliest stage (approximately 2 h) of significant induction of lymphocyte entry by TNF-alpha and IL-1 alpha the inductive signal for each appears easily saturated. Thus lymphocyte entry is little increased by increasing low cytokine doses over 100-fold: However, these reactions are additive, and this was used to confirm that they are distinct from each other and from PHA. A further distinction was revealed by the homing of lymphocytes pretreated with pertussis toxin: such lymphocytes were greater than 90% inhibited in their homing to tissues through constitutive high endothelial venules (HEV) and greater than 60% inhibited in homing to TNF-alpha and IL-1 alpha skin sites, but unaffected in homing to PHA skin sites (like most non-HEV-mediated traffic). Moreover, potent chicken anti-TNF-alpha, which prevented TNF-induced lymphocyte entry, did not affect PHA-induced traffic. Thus, these three agents which induce peripheral lymphocyte traffic appear to involve different mechanisms as shown by differences in (i) their kinetics; (ii) the effect of anti-TNF-alpha and (iii) the effect of pertussis toxin treatment of the lymphocytes and by the fact that their inductive mechanisms are additive in effect.
Eur J Immunol 1992 Sep
PMID:Active lymphocyte traffic induced in the periphery by cytokines and phytohemagglutinin: three different mechanisms? 151 13

Chemoattractant-induced activation of human polymorphonuclear leukocytes involves receptor coupling to guanine nucleotide binding proteins (G-proteins). Treatment of polymorphonuclear leukocytes with pertussis toxin, which ADP-ribosylates neutrophil G-proteins and uncouples G-proteins from receptors, causes a conversion of cells from responders to nonresponders rather than a gradual decrease in the ability of all cells to respond (Omann, G. M., and J. M. Harter. 1991. Cytometry 12:252; Omann, G. M., and M. M. Porasik-Lowes. 1991. J. Immunol. 146:1303). Flow-cytometric methods were used to measure N-formylpeptide-induced cytosolic Ca2+ elevation and actin polymerization over a wide range of ADP-ribosylation levels and showed that although the percentage of responding cells varied markedly, the responding cells were stimulated equivalent to controls. The conditions of pertussis toxin (PT) treatment did not interfere with non-G-protein-mediated pathways as assessed by measurement of phagocytosis, a complex process involving the cytoskeleton. We tested the explanation that the all-or-none effect may have been due to heterogeneous insertion of the catalytic subunit of PT into the cells such that responders had no ADP-ribosylation and nonresponders were completely ADP-ribosylated. Measurement of the binding of fluorescent N-formylpeptides to permeabilized cells, which allows the distinction between completely ribosylated and normal cells, showed that all cells treated with a submaximal concentration of PT had intermediate levels of receptor-coupled G-proteins. Thus, partial ADP-ribosylation had occurred in all cells and the all-or-none insertion of the catalytic subunit of PT was ruled out. Thus, there is a threshold of coupled G-proteins required to transduce responses. The ability of PT to inhibit N-formylpeptide-induced actin polymerization and cytosolic calcium elevation was compared and showed that both responses have essentially the same threshold of G-proteins required to transduce the responses. Thus, the pathways regulating actin polymerization and calcium elevation appear to be coupled with equal efficiency to the G-proteins.
J Immunol 1992 Sep 15
PMID:A threshold level of coupled G-proteins is required to transduce neutrophil responses. 151 77

The G-protein Gi is known to mediate signal transduction in cells by coupling its 41 kDa alpha-subunit to plasma membrane-bound receptors and inhibiting adenylyl cyclase or affecting ion channel function. Although this G-protein has been functionally associated with D2/dopamine and mu-opioid receptors in striatal membranes, its localization to neurons of the neostriatum, a brain region rich in adenylyl cyclase activity, has not been established. Light and electron microscopic study of the basal ganglia was conducted using the immunoperoxidase method and an antiserum directed against the alpha-subunit of Gi. In the neostriatum, immunoreactivity was localized to medium-sized spiny and aspiny neurons and axon terminals that formed symmetric synapses. Some astrocytes and glial processes that encapsulated axospinous complexes were also labeled. Immunoreactive axon terminals were numerous in the globus pallidus and substantia nigra, where they exhibited a dense pattern of distribution characteristic of neostriatal spiny projection neurons. Gi alpha immunoreactivity was distributed to multiple subcellular compartments. In neostriatal somata and dendrites, labeling was present intermittently along plasma membranes, and on rough and smooth endoplasmic reticulum and microtubules. In axon terminals, reaction product appeared on plasma membranes and heavily labeled the membranes of synaptic vesicles. The presence of Gi alpha in axon terminals was confirmed in purified synaptosome preparations. G-proteins consistent with the masses of Go alpha and Gi alpha, respectively, were ADP-ribosylated in the presence of pertussis toxin in striatal synaptosomes. Western blot analysis in purified synaptosome preparations of the neostriatum, globus pallidus, and substantia nigra with the same antiserum used in the immunohistochemistry demonstrated a predominant 41 kDa protein corresponding to the molecular mass of Gi alpha. Immunohistochemical localization of Gi alpha with the immunogold method in a crude striatal synaptosome preparation showed gold particles associated with synaptic vesicles and plasma membranes. Results provide the first direct evidence that Gi alpha is localized to medium-sized neostriatal projection neurons and interneurons, where it is likely to function in membrane-bound signal transduction at the postsynaptic and presynaptic level. The presence of Gi alpha in synaptic vesicle membranes points to another potentially important role for this G-protein in vesicle trafficking, such as that recently shown for smaller-molecular-mass G-proteins.
J Neurosci 1992 Sep
PMID:The subcellular localization of the G-protein Gi alpha in the basal ganglia reveals its potential role in both signal transduction and vesicle trafficking. 152 88

The effect of adenosine on phosphoinositide hydrolysis was examined in 1321N1 human astrocytoma cells. Adenosine, L-N6-phenylisopropyladenosine (L-PIA), and 5'-(N-ethylcarboxamido)adenosine (NECA) inhibited histamine-stimulated accumulation of inositol phosphates in a concentration-dependent manner. The potency order of adenosine analogues for inhibition of inositol phosphate accumulation was L-PIA greater than adenosine greater than NECA, a finding indicating that A1-class adenosine receptors are involved in the inhibition. The reduction in inositol phosphate accumulation by L-PIA was blocked by an adenosine receptor antagonist, 8-phenyltheophylline. Stimulation of A1-class adenosine receptors inhibited isoproterenol-stimulated cyclic AMP accumulation as well as histamine-induced inositol phosphate accumulation. Both inhibitory effects were blocked by pretreatment of the cells with pertussis toxin [islet-activating protein (IAP)]. L-PIA also inhibited guanosine 5'-(gamma-thio)triphosphate (GTP gamma S)-stimulated accumulation of inositol phosphates in membrane preparations, and 8-phenyl-theophylline antagonized the inhibition. L-PIA could not inhibit GTP gamma S-induced accumulation of inositol phosphates in IAP-treated membranes. Gi/Go, purified from rabbit brain, inhibited GTP gamma S-stimulated accumulation of inositol phosphates in a concentration-dependent manner in membrane preparations. These results suggest that stimulation of A1-class adenosine receptors interacts with the IAP-sensitive G protein(s), resulting in the inhibitions of phospholipase C as well as adenylate cyclase in human astrocytoma cells.
J Neurochem 1991 Sep
PMID:Adenosine inhibits histamine-induced phosphoinositide hydrolysis mediated via pertussis toxin-sensitive G protein in human astrocytoma cells. 165 Mar 98

In the present work we evaluated the interactions of adrenergic receptors with phospholipase-C (PLC) and protein kinase-C (PKC), using an in vitro system of hypothalamic neurons and astroglial cells in primary cultures. The study was performed on immature neurons after 7 days in vitro (7 Div), that is before synaptogenesis, as well as on mature cells (14 Div). Comparisons were made between neurons and glial cells at the corresponding developmental stages. Norepinephrine (NE) increased inositol phosphates (IPs) formation in a dose- and time-dependent manner. The NE effect was mediated by alpha 1-receptor (alpha 1R) and was observed in young cells before synaptogenesis as well as in mature neuronal cultures; its amplitude was enhanced during the latter stage of the neuronal development. The coupling of alpha 1R with PLC was partially sensitive to pertussis toxin treatment and did not implicate the activation of calcium voltage-dependent channels. Activation of PKC by 12-O-Tetradecanoylphorbol 13-acetate (TPA) inhibited in a time-dependent manner the NE-stimulated production of IPs in young and mature hypothalamic neurons; however, in PKC depleted cells NE-induced IPs formation remained unchanged. In hypothalamic astroglial cell cultures the adrenergic stimulus of IPs generation was also mediated by alpha 1R. The effect was observed at both developmental stages, with a greater response in 14 Div cultures, and was insensitive to pertussis toxin treatment. As in neurons, activation of PKC resulted in inhibition of NE-induced IPs formation. These data indicate that functional interrelation between alpha 1R, PLC, and PKC is already present in immature neurons and glial cells and progressively develops in culture.
Endocrinology 1991 Sep
PMID:Alpha 1-adrenergic receptor coupling with phospholipase-C is negatively regulated by protein kinase-C in primary cultures of hypothalamic neurons and glial cells. 165 54

The effects of holotoxins and toxin subunits from Bordetella pertussis and Vibrio cholerae strains on intact and digitonin-permeabilized human polymorphonuclear neutrophils were studied. Our data clearly demonstrate that formyl-methionyl-leucyl-phenylalanine (fMLP)-induced generation of chemotactic active leukotriene B4 was inhibited by both holotoxins as well as by their isolated enzymatic A protomers. In contrast, the respective binding components (B oligomers) did not affect leukotriene formation. Priming of digitonin-permeabilized neutrophils with either guanylylimidodiphosphate or inositol trisphosphate increased subsequent stimulation with fMLP. In contrast, diacylglycerol decreased fMLP-induced leukotriene B4 formation, but inositol trisphosphate and diacylglycerol had no effect on inhibition mediated by the toxins. In addition, pertussis and cholera toxins reduced the specific binding of [3H]fMLP. Scatchard plot analysis revealed that the observed decrease of peptide binding was due to a reduced number of receptor sites. The fMLP-stimulated [3H]guanylylimidodiphosphate binding and GTPase activity used as parameters for the activation of G proteins were decreased in parallel. These results suggest altered chemotactic receptor numbers and G-protein functions responsible for the toxin-dependent suppression of fMLP-mediated response for neutrophils.
Infect Immun 1991 Sep
PMID:Regulation of leukotriene B4 generation from human polymorphonuclear granulocytes after stimulation with formyl-methionyl-leucyl phenylalanine: effects of pertussis and cholera toxins. 165 58

Bacteroides spp. may contribute to the chronicity of mixed infections by affecting the normal functions of polymorphonuclear leukocytes (PMN). This study evaluated the physiologic and biochemical responses of human peripheral blood PMN to a variety of strains of the oral periodontal pathogen Porphyromonas (Bacteroides) gingivalis. Strain 381 and ATCC type strain 33277 caused rapid and lasting depolarization of the electrochemical potential that exists across the PMN membrane by a mechanism that was independent of activation of the pertussis toxin-sensitive G protein or protein kinase C. Membrane depolarization did not initiate increases in intracellular calcium or respiratory burst activation, and activity was not inhibited by surface proteolysis or sugars. However, membrane depolarization was associated with inhibition of PMN responses to the chemotactic peptide N-formylmethionyl leucyl phenylalanine. Membrane-depolarizing activity was isolated with the outer membrane of strain 381 by surface extraction of the bacteria by using Zwittergent 3,14, followed by Sephacryl S-200 gel filtration chromatography. The partially purified outer membrane components were heat stable, were not inhibited by tosyl-lysine chloromethyl ketone, and inhibited N-formylmethionyl leucyl phenylalanine-stimulated superoxide production. The results suggest that outer membrane components of P. gingivalis 381 and 33277 have porinlike activity that can depolarize PMN membranes and immobilize PMN responses to chemotactic peptides. This may prove to be an important virulence characteristic of these strains.
Infect Immun 1991 Sep
PMID:Depolarization of polymorphonuclear leukocytes by Porphyromonas (Bacteroides) gingivalis 381 in the absence of respiratory burst activation. 165 60


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>