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)

Lysozyme release from purified human polymorphonuclear leukocytes was found to be uniquely enhanced by 2.5-20 mM LiCl. This effect was dose dependent and was not detected when the media was supplemented with NaCl, KCl, MgCl2, or CaCl2. The purified isotopes of Li+, 6Li, and 7Li were equally effective in enhancing lysozyme release from the cells at 10 and 20 mM, but 6Li was more effective than 7Li at 5 mM. The enhancement of enzyme release in the presence of Li+ was comparable to the enhancement observed in the presence of N-formylmethionylleucylphenylalanine (fMLP). Addition of LiCl plus fMLP did not result in lysozyme release in excess of each stimulant alone, except when the cells were incubated with 20 mM 6Li + 10(-5) M fMLP. In addition, enzyme release induced by these two agents could be further enhanced to the same degree by addition of cytochalasin D to the incubation mixtures. While similarities between enzyme release induced by LiCl and fMLP were detected, optimal stimulation of enzyme release by Li+ was much more sensitive to inhibition by pertussis toxin than was maximal fMLP stimulation. Therefore, the intracellular events altered by Li+ and the peptide may share some metabolic steps, but they differ in their sensitivity to alterations in cAMP metabolism.
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PMID:Characterization of lithium-induced enzyme release from human polymorphonuclear leukocytes. 377 61

We compared the effects of guanine nucleotides and Mg2+ on ADP-ribosylation of rat brain and liver membrane proteins catalysed by Bordetella pertussis toxin (IAP) and cholera toxin (CT). Labelling of proteins in the presence of [alpha-32P]NAD+, ATP and CT required GTP or guanosine 5'-[gamma-thio]triphosphate (GTP [S]). In contrast, labelling of one (liver) or two (brain) polypeptides by IAP was enhanced by guanosine 5'-[beta-thio]diphosphate (GDP[S]) or GTP, but was blocked by GTP[S] or guanosine 5'-[beta, gamma-imido]triphosphate (p[NH]ppG). The order of labelling intensity was GDP[S] greater than GTP greater than no addition greater than GTP[S] = p [NH]ppG. Mg2+ increased labelling by CT, but decreased labelling by IAP. In addition, Mg2+ potentiated the effects of the guanine nucleotides, increasing the inhibitory effects of GTP[S] and the activatory effects of GDP[S] or GTP. Preincubating liver membranes at 30 degrees C in the presence of 10 mm-MgCl2 inhibited labelling by IAP irreversibly. Pretreatment of liver membranes with 4.95 mM-N-ethylmaleimide decreased labelling by CT by approximately 15%, but almost completely blocked labelling by IAP. These results suggest that the undissociated, GDP-bound, conformation of Ni, the inhibitory GTP-binding protein of adenylate cyclase, is the preferred substrate for ADP-ribosylation by IAP. This conformation, which is prevalent in native membranes, is sensitive to temperature, Mg2+ ions and alkylating agents such as N-ethylmaleimide. At 30 degrees C, Mg2+ may cause dissociation and denaturation of Ni in native membranes.
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PMID:Pertussis toxin substrate is a guanosine 5'-[beta-thio]diphosphate-, N-ethylmaleimide-, Mg2+- and temperature-sensitive GTP-binding protein. 393 83

A single-step chromatography on Matrex-Gel Blue A has been employed to obtain soluble extracts containing some of the most important antigens of Bordetella pertussis, pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (69-kDa outer membrane protein), fimbriae (FIM2 and FIM3) and adenylate cyclase (AC). Two supernatants, P19 (48.8 mg PT, 6.8 mg FHA, 17.3 mg AC, 13 mg FIM2 and 4.9 mg FIM3 per liter) and P21 (0.1 mg PT, 0.07 mg FHA, 0.46 mg FIM2 and 0.94 mg FIM3 per liter), resulting from bacteria grown in Stainer-Scholte medium, were submitted to chromatography. Fractions with the antigens were obtained after stepwise elution with 60 mM sodium phosphate buffer, pH 6.0; 50 mM Tris-HCl, pH 7.4; 50 mM Tris-HCl, pH 7.4/0.75 M MgCl2; 50 mM Tris-HCl, pH 7.4/4 M MgCl2 and 4 M urea. Preparations from P19 (containing 4.05 micrograms PT, 8.14 micrograms FHA, 6.3 micrograms AC, 3.37 micrograms 69-kDa, 9.54 micrograms FIM2 and 2.23 micrograms FIM3) and from P21 (with 0.175 micrograms PT, 0.28 micrograms FHA, 0.002 micrograms 69-kDa, 0.005 micrograms FIM2 and 0.122 micrograms FIM3) were detoxified with glutaraldehyde and tested as an acellular pertussis vaccine. These products were non-toxic for mice and induced high levels of antibodies against purified pertussis antigens, as judged by ELISA.
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PMID:A Bordetella pertussis acellular vaccine candidate: antigenic characterization and antibody induction. 754 83

We previously reported that pertussis toxin (PTX) had little effect on arginine vasopressin-induced formation of inositol trisphosphate (IP3) in rat aortic smooth muscle cells [Kondo et al.: Biochemical and Biophysical Research Communications 161:677-682, 1989]. In the present study, we investigated the mechanism of vasopressin-induced arachidonic acid release in rat aortic smooth muscle cells. Vasopressin stimulated both the release of arachidonic acid and the formation of IP3 dose dependently in the range between 10 pM and 1 microM. The effect of vasopressin on arachidonic acid release was more potent than that on the formation of IP3. Quinacrine, a phospholipase A2 inhibitor, significantly suppressed the vasopressin-induced arachidonic acid release but had little effect on the formation of inositol phosphates. NaF, a GTP-binding protein activator, mimicked vasopressin by stimulating the arachidonic acid release. The arachidonic acid release stimulated by a combination of vasopressin and NaF was not additive. PTX partially but significantly suppressed the vasopressin-induced arachidonic acid release. In the cell membranes, PTX catalyzed ADP-ribosylation of a protein with an M(r) of about 40,000. Pretreatment of membranes with 0.1 microM vasopressin in the presence of 2.5 mM MgCl2 and 100 microM GTP markedly attenuated this PTX-catalyzed ADP-ribosylation of the protein in a time-dependent manner. These results strongly suggest that PTX-sensitive GTP-binding protein is involved in the coupling of vasopressin receptor to phospholipase A2 in primary cultured rat aortic smooth muscle cells.
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PMID:Vasopressin induces arachidonic acid release through pertussis toxin-sensitive GTP-binding protein in aortic smooth muscle cells: independence from phosphoinositide hydrolysis. 822 89

The activity of a hormone- and growth-factor-stimulated NADH oxidase of the rat liver plasma membrane responds to guanine nucleotides, but in a manner that differs from that of the classic trimeric and low-molecular-mass monomeric G-proteins. In the absence of added bivalent ions, both GTP and GDP as well as guanosine 5'-[gamma-thio]triphosphate (GTP[gamma-S]) but not guanosine 5'[beta-thio]diphosphate (GDP[beta-S]) stimulate the activity over the range 1 microM to 100 microM. Other di- and tri-nucleotides also stimulate, but only at concentrations of 100 microM or higher. Added bivalent ions are not required either for NADH oxidation or guanine nucleotide stimulation. Bivalent ions (Mg2+ > Mn2+ > or = Ca2+) alone stimulate only slightly at low concentrations and then inhibit at high concentrations. The inhibitions are augmented by GDP or GTP [gamma-S] but not by GTP. Although the activity is the same, or less, in the presence of 0.5 mM MgCl2, GTP at 1-100 nM and other nucleotides at 0.1 mM or 1 mM still stimulate in its presence. The NADH oxidase is activated by mastoparan but aluminum fluoride is weakly inhibitory. Cholera and pertussis toxins elicit only marginal responses. Both the Mg2+ and the GDP and GTP[gamma-S] inhibitions (but not the GTP stimulations) shift to higher concentrations when the membrane preparations are first solubilized with Triton X-100. The results suggest a role for guanine nucleotides in the regulation of plasma membrane NADH oxidase, but with properties that differ from those of either trimeric or the low-molecular-mass G proteins thus far described.
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PMID:NADH oxidase activity of rat liver plasma membrane activated by guanine nucleotides. 831 95

1. The activation of G proteins by type 1alpha metabotropic glutamate receptors (mGluRs) in membranes from recombinant baby hamster kidney cells expressing the cloned rat mGluR1alpha receptor has been studied by use of a [35S]-guanosine 5'-[gamma-thio]triphosphate ([35S]-GTPgammaS) binding assay. 2. L-Glutamate increased the rate of [35S]-GTPgammaS binding in a concentration-dependent manner (-logEC50 (M) 5.25 +/- 0.07), with an optimal (62.4 +/- 1.6%) increase over basal binding being observed following 60 min incubation at 30 degrees C with 70 pM [35S]-GTPgammaS, 1 microM GDP, 10 mM MgCl2, 100 mM NaCl and 100 microg membrane protein ml(-1). The L-glutamate (100 microM)-stimulated increase in [35S]-GTPgammaS binding was totally prevented in the presence of the group I mGluR antagonist (S)-4-carboxy-3-hydroxyphenylglycine (300 microM). 3. Quantitative analysis of the affinity and number of G proteins activated by a maximally effective concentration of L-glutamate revealed an equilibrium dissociation constant (K(D)) for [35S]-GTPgammaS binding of 0.76 +/- 0.20 nM and a maximal number of GTPgammaS-liganded G proteins (Bmax) of 361 +/- 30 fmol mg(-1) protein. 4. Metabotropic glutamate receptor agonists, quisqualate (-logEC50 (M) 6.74 +/- 0.06), 1S,3R-ACPD (4.64 +/- 0.08) and (S)-3,5-dihydroxyphenylglycine (5.16 +/- 0.23) also increased [35S]-GTPgammaS binding in a concentration-dependent manner, with the latter two agents behaving as partial agonists. 5. (+)-alpha-Methylcarboxyphenylglycine (300 microM) caused a parallel rightward shift of the L-glutamate concentration-effect curve for [35S]-GTPgammaS binding, allowing an antagonist equilibrium dissociation constant (K(D)) of 34.0 +/- 7.8 microM to be calculated for this mGluR antagonist. 6. Pretreatment of BHK-mGluR1alpha cells with a concentration of pertussis toxin (PTX) shown to be maximally effective (100 ng ml(-1), 24 h) before membrane preparation resulted in a marked decrease in agonist-stimulated [35S]-GTPgammaS binding (by 66.0 +/- 0.9%), and an altered concentration-effect relationship for agonist-stimulated [35S]-GTPgammaS binding by the residual PTX-insensitive G-protein population. 7. The modulation of [35S]-GTPgammaS binding by agonists and antagonists in membranes from recombinant cells provides an excellent system in which to study mGluR interactions with PTX-sensitive and -insensitive G proteins.
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PMID:Pharmacological characterization of type 1alpha metabotropic glutamate receptor-stimulated [35S]-GTPgammaS binding. 924 58

The activation of G-proteins by melatonin mt1 receptors was studied by measuring [35S]-guanosine-5'-(3-thiotriphosphate) ([35S]-GTPgammaS) binding to membranes prepared from Chinese hamster ovary (CHO) cells stably expressing human mt1 receptors. Melatonin stimulated [35S]-GTPgammaS binding in a concentration-dependent manner (pEC50, 8.77+/-0.02). The optimal (212+/-4%) increase over basal levels of binding (basal = 100%) was observed following incubation of membranes (12.5 microg protein/well) for 120 min at 30 degrees with [35S]-GTPgammaS (0.1 nM), in the presence of GDP (10 microM), NaCl (100 mM), and MgCl2 (10 mM). Melatonin analogues stimulated [35S]-GTPgammaS binding with a rank order (2-iodomelatonin > melatonin = S20098 > GR196429 > 6-chloromelatonin = 6-hydroxymelatonin >> N-acetylserotonin > or = GR135531 = mt1 luzindole = 5-HT = 0), which was identical to their affinities for the high affinity state of the receptor (correlation coefficient 0.94). All agonists evoked similar maximum increases in [35S]-GTPgammaS binding. EC50 values were 14- to 63-fold lower than binding affinities. The melatonin receptor antagonist luzindole (0.1-10 microM) evoked a parallel rightward shift in the melatonin concentration-response curve, with a pKB of 7.19+/-0.13, which is similar to its affinity in radioligand binding studies for human mt1 receptors. Stimulation of [35S]-GTPgammaS binding was abolished by pretreatment of cells with pertussis toxin (18 hr, 100 ng/mL) prior to preparation of membranes. Melatonin was without effect in CHO cells which lacked the mt1 receptor. Thus, melatonin and melatonin analogues stimulate [35S]-GTPgammaS binding with a profile which is consistent with binding to mt1 receptors causing activation of Gi/Go G-proteins.
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PMID:Pharmacological characterisation of melatonin mt1 receptor-mediated stimulation of [35S]-GTPgammaS binding. 980 27

The underlying molecular mechanism of action of lithium in the treatment of manic-depressive illness is not clear. The effect of chronic lithium on GTP-binding and toxin-mediated ADP-ribosylation of specific G proteins in brain cortical membranes was examined. Incubation of cortical membranes with 5-HT increased [35S]GTPgammaS binding to Galphas, Galphai, Galphao and Galphaq proteins. Six weeks but not 1 week of lithium treatment reduced the increases in [35S]GTPgammaS binding to Galphas, Galphai and Galphao which are produced by 5-HT by 75-85%, whereas 5-HT stimulated [35S]GTPgammaS binding to Galphaq was reduced by 38%. No changes in membrane levels of Galpha and Gbeta proteins were noted in lithium-treated rats. Pertussis toxin (PTX)-mediated ADP-ribosylation of Galphai/o was increased by 60% in cortical membranes of chronically treated rats. Lithium treatment did not affect cholera toxin-mediated ribosylation of Galphas. Increases in [35S]GTPgammaS binding to Galpha proteins evoked by 5-HT were also inhibited by 0.5-2.0 mM lithium chloride added in vitro to the assay mixture. Rubidium and cesium did not change 5-HT-stimulated G protein activation. ADP-ribosylation of Galphai/o catalyzed by PTX was not changed by in vitro LiCl. The inhibitions of 5-HT-stimulated increases in [35S]GTPgammaS-binding to Galphas and Galphaq were completely suppressed by 2.4 mM MgCl2 this concentration of MgCl2 inhibited the effect of lithium on Galphai and Galphao by 50%. Similar findings were also noted when [alpha-32P]GTP was used in the binding assay. The results suggest that lithium interferes with receptor-G protein coupling via a Mg2+-sensitive mechanism. This action of the drug is more effective for Gs, Gi and Go than for Gq and may result from its interference with the recycling of trimeric G proteins.
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PMID:Effects of lithium on receptor-mediated activation of G proteins in rat brain cortical membranes. 1021 78

Bordetella pertussis dramatically alters its phenotype by sensing its environment via the BvgAS regulatory system. Increased concentrations of specific chemicals are used in vitro to induce modulation of the bacterium from the Bvg(+) virulent phenotype to a fully Bvg(-) phenotype. Varied expression of sets of Bvg(-)regulated molecules depends on the modulating capacity of the environment. We examined the effect of a number of chemicals on the modulating capacity of B. pertussis growth media, both alone and in combination with known modulators. It was demonstrated that under certain conditions the Bvg(-)intermediate protein, BipA, is coexpressed with the Bvg(-) antigen, VraA. This demonstrates that the patterns of molecules expressed in the different phenotypes of B. pertussis are more fluid than has previously been demonstrated. The in vitro modulator, sulfate, was found to be a relatively inefficient modulator of our Tohama I-derived B. pertussis strain. However, addition of nicotinic acid, MgCl2, or sucrose in combination with relatively low sulfate concentrations resulted in effective modulation. This suggests that multiple signals may affect modulation through the BvgAS system or possibly through other regulatory networks. In addition, the cooperative modulating effect of sucrose implicates osmolarity as an environmental stimulus that affects phenotypic modulation.
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PMID:Osmolarity affects Bvg-mediated virulence regulation by Bordetella pertussis. 1802 26


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