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)

Calcium currents can be modulated by receptor activation of the GTP-binding protein G(o). We have determined whether the two forms of G(o), Go1 and Go2, differentially regulate calcium current magnitude. Using identified neurons of the pond snail Helisoma, we demonstrate that a high-voltage-activated (HVA) calcium current is reduced by addition of the neuropeptide Phe-Met-Arg-Phe-amide (FMRFamide) and that this inhibition is mediated by a pertussis toxin (PTX)-sensitive G protein pathway. Using this calcium current as an assay for G protein activity, we microinjected GTP gamma S-activated alpha-subunits of G proteins into neuronal somata. We demonstrate that the calcium current is differentially regulated by the two forms of alpha o. Microinjection of alpha o2*, but not alpha o1*, reduces calcium current magnitude.
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PMID:Microinjection of the alpha-subunit of the G protein Go2, but not Go1, reduces a voltage-sensitive calcium current. 141 84

In this study, we have used photoaffinity labeling by [32P]azido-GTP as well as [32P]ADP-ribosylation by pertussis toxin (PT) and cholera toxin (CT) to identify GTP-binding proteins associated with mouse T-lymphoma plasma membranes. Our results indicate that GP85 (CD44) can be photoaffinity labeled by [32P] azido-GTP and [32P]ADP-ribosylated by both PT and CT. Using purified GP85 (CD44) obtained by Triton X-100 extraction, wheat germ agglutinin-Sepharose, and anti-GP85 (CD44) antibody affinity chromatographies, we have further characterized GP85 (CD44) as a GTP-binding protein. GP85 (CD44) is found to bind guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) in a time- and dose-dependent manner with a dissociation constant of 0.83 nM. Importantly, GP85 (CD44) appears to display a GTPase activity which hydrolyzes [gamma-32P]GTP at a rate of 0.011 mol of Pi released/mol of GP85 (CD44)/min. This GTPase activity can be readily inhibited by PT- or CT-mediated ribosylation of GP85 (CD44). Most interestingly, GTP binding significantly enhances the interaction of purified GP85 (CD44) with ankyrin, whereas ADP-ribosylation of GP85 (CD44) by PT or CT inhibits the GTP-induced increase in ankyrin binding to GP85 (CD44). In addition to GP85 (CD44) being the first reported transmembrane GTP-binding protein, these results suggest that GTP plays an important role in promoting the interaction between GP85 (CD44) and its underlying membrane cytoskeleton through ankyrin.
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PMID:The lymphoma transmembrane glycoprotein GP85 (CD44) is a novel guanine nucleotide-binding protein which regulates GP85 (CD44)-ankyrin interaction. 142 59

We have examined the possible involvement of pertussis toxin (PT)-sensitive GTP-binding protein and protein kinase C (PKC) in mitogen-induced tyrosine phosphorylation of the 41 kDa and 43 kDa cytosol proteins using PT-pretreated (inactivation of PT-sensitive GTP-binding protein) or phorbol 12-myristate 13-acetate (PMA)-pretreated (depletion of PKC) mouse fibroblasts. The effects of the inactivation of PT-sensitive GTP-binding protein and the depletion of PKC on mitogen-stimulated tyrosine phosphorylation of the proteins were similar and varied significantly and systematically in response to growth factors. The important finding was that such inhibitory effects of PT-sensitive GTP-binding protein inactivation and PKC depletion on protein tyrosine phosphorylation induced by each mitogen always correlated well with their inhibitory effects on each mitogen-stimulated DNA synthesis. Although the extent of platelet-derived-growth-factor-induced phosphorylation of the proteins was decreased to approx. 50% in PT- and PMA-pretreated cells compared with native cells, protein phosphorylation itself was not affected and occurred at identical sites on each protein in native, PT- and PMA-pretreated cells. These results suggest that: (1) 41 kDa and 43 kDa proteins are located downstream of PT-sensitive GTP-binding protein and PKC in the mitogenic signalling pathways of growth factors, (2) protein phosphorylation occurs via a cascade of events which includes the activation of the receptor tyrosine kinases, PKC and other unidentified kinase(s) which directly participate(s) in the phosphorylation of the 41 kDa and 43 kDa proteins, and (3) their phosphorylation may play an important role in integrating multiple mitogenic signalling pathways.
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PMID:Mitogen-induced tyrosine phosphorylation of 41 kDa and 43 kDa proteins. Potential role in integrating multiple mitogenic signalling pathways. 144 50

The ADP-ribosyl moiety of NAD was transferred to a 40-kDa protein when rat liver nuclei were incubated with pertussis toxin. The 40-kDa substrate in the nuclei displayed unique properties as follows, some of which were apparently distinct from those observed with the toxin-substrate GTP-binding protein (Gi) in the liver plasma membranes. 1) The nuclear 40-kDa protein was recognized with antibodies reacting with the alpha-subunits (alpha i-1 and alpha i-2) of Gi, but not with anti-Go-alpha-subunit antibody. 2) The nuclear protein had a higher mobility than alpha-subunit of the plasma membrane-bound Gi upon electrophoresis with a urea/sodium dodecyl sulfate-containing polyacrylamide gel. 3) The nuclear protein was not extracted from the nuclei with 1% Triton X-100, whereas Gi was easily solubilized from the plasma membranes. 4) There was a beta gamma-subunit-like activity in the nuclei, which was assayed by an ability to support pertussis toxin-catalyzed ADP-ribosylation of a purified alpha-subunit of Gi. Moreover, a 36-kDa protein in the nuclei was recognized with antibody raised against purified beta-subunits of Gi. 5) Pertussis toxin-induced ADP-ribosylation of the nuclear protein was selectively inhibited by the addition of a nonhydrolyzable GTP analogue, and its inhibitory action was competitively blocked by the simultaneous addition of GDP or its analogues, as had been observed with plasma membrane-bound Gi. It thus appeared that a novel form of alpha beta gamma-trimeric GTP-binding protein serving as the substrate of pertussis toxin was present in rat liver nuclei. In order to examine a possible role of the nuclear GTP-binding protein, rats were injected with carbon tetrachloride, a necrosis inducer of hepatocytes. There was a marked increase in the nuclear substrate activity from 3-6 days after the injection, without a significant change in the activity of Gi in the plasma membranes. The time course of the increase corresponded with a recovering stage from the hepatocyte necrosis. These results suggested that the nuclear GTP-binding protein found in the present study might be involved at some stages in the hepatocyte growth.
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PMID:A GTP-binding protein in rat liver nuclei serving as the specific substrate of pertussis toxin-catalyzed ADP-ribosylation. 154 91

Activation of neutrophils was recently reported to be accompanied by large changes in their Cl- content [J. B. Myers, H. F. Cantiello, J. H. Schwartz, and A. I. Tauber. Am. J. Physiol. 259 (Cell Physiol. 28): C531-C540, 1990]. The significance of these ionic changes to the immune response has not been studied. To evaluate the role of intracellular [Cl-], the anionic composition of the cytosol was varied in human neutrophils permeabilized by electroporation or by treatment with streptolysin O. In Cl(-)-rich media, permeabilized but otherwise untreated cells remained quiescent, resembling unstimulated intact cells. In contrast, suspension of permeabilized cells in Cl(-)-depleted media elicited protein phosphorylation, actin polymerization, secretion of lysozyme, and a respiratory burst. The latter was demonstrated by several criteria to be mediated by the NADPH oxidase. The responses observed in Cl(-)-depleted media were insensitive to pretreatment of the cells with pertussis toxin but were inhibited by addition of GDP or by omission of ATP. The data suggest that an early event in signal transduction, common to several effectors, is sensitive to the ionic composition of the cytosol. This component, possibly a GTP-binding protein, may be affected by the anion concentration changes reported to occur during physiological stimulation of neutrophils.
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PMID:Activation of permeabilized neutrophils: role of anions. 163 84

In cloned osteoblast-like cells, MC3T3-E1, prostaglandin E2 (PGE2) stimulated the formation of inositol phosphates in a dose-dependent manner in the range between 10 nM and 10 microM. Pertussis toxin inhibited the effect of PGE2 dose-dependently in the range between 1 ng/ml and 1 micrograms/ml. In the cell membranes, pertussis toxin catalyzed ADP-ribosylation of a protein with an Mr of about 40,000. Pretreatment of membranes with 10 microM PGE2 in the presence of 2.5 mM MgCl2 and 100 microM GTP markedly attenuated this pertussis toxin-catalyzed ADP-ribosylation of the protein in a time-dependent manner. G12 was detected in these cells by immunoblotting with purified anti-G12 alpha antibodies. The results indicate the possible coupling of PGE2 signalling with pertussis toxin-sensitive GTP-binding protein, which is probably G12, in osteoblast-like cells.
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PMID:Possible coupling of prostaglandin E2 receptor with pertussis toxin-sensitive guanine nucleotide-binding protein in osteoblast-like cells. 165 Jul 71

We examined effects of acetylcholine (ACh) on isoproterenol (ISP)-induced changes of the upstroke velocity of the action potential (Vmax) in isolated 13.5 mM K(+)-depolarized atrial muscles from guinea-pigs, using conventional glass microelectrode techniques. In some experiments, ventricular muscles were also used, for purposes of comparison. ISP (0.1 microM) decreased the fast component of Vmax (Vmax,fast) and increased the slow component of Vmax (Vmax, slow) of the atrial muscle, as has been noted in ventricular muscle. ACh (0.1 microM) reversed or antagonized these effects of ISP. However, in the presence of atropine (0.1 microM), the antagonism disappeared. In the presence of the Ca2+ channel blocker, D600 (1 microM), the depressant effect of ISP on the Vmax,fast was augmented while ACh exerted a much less restorative effect on the ISP-induced, depressed Vmax,fast. Similar findings were obtained in low (0.36 and 0.072 mM) Ca2+ media. To investigate the possible involvement of GTP-binding protein (Gi) on these ACh effects, we performed similar experiments using atrial muscles obtained from guinea pigs pre-treated with pertussis toxin (150 micrograms/kg) for 48 h. In these preparations, the depressant effect of ISP on the Vmax,fast remained unaffected, while the reversing effect of ACh on the ISP-induced depression of Vmax,fast either specifically diminished or disappeared. These results show that ACh antagonizes the ISP-induced Vmax changes via stimulation of muscarinic ACh receptors and that this effect is presumably mediated by Gi and modified by intracellular Ca2+. Clinical implications are discussed.
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PMID:Acetylcholine reverses isoproterenol-induced depression of Vmax in residual Na channel-dependent action potentials of guinea-pig cardiac muscles. 165 59

1. The membrane currents evoked by glutamate agonists on isolated and identified neurones of molluscan pedal ganglia were investigated using the voltage clamp technique. 2. The fast chloride current (Er (reversal potential) = -41 mV) evoked in a Ped-9 neurone by application of glutamate, quisqualate and ibotenic acid could be blocked by furosemide (0.1 mM). The slow potassium current (Er = -85 mV) evoked in Ped-8 and Ped-9 neurones by glutamate, quisqualate and kainate could be blocked by tetraethylammonium (50 microM). 3. N-Methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA) failed to induce a response in neurones studies. 4. The spider venoms argiopine and argiopinine III (50-500 nM) selectively inhibited quisqualate-induced potassium current, but had no influence on glutamate-, ibotenate- or quisqualate-induced chloride and kainate-induced potassium currents. Glutamate-induced potassium current was partially inhibited by argiopine and argiopinine III. 5. The existence of several types of distinct glutamate receptors was confirmed in cross-desensitization experiments, and a lack of interaction was observed between quisqualate and kainate. 6. Potassium currents induced both by quisqualate and kainate strongly depended on temperature and could be blocked by pertussis toxin. Intracellular injection of the calcium chelator, EGTA, did not affect quisqualate and kainate responses. 7. In neurones loaded with non-hydrolysable GTP analogues, GTP-gamma-S (guanosine-5'-O-(3-thio)triphosphate) or GppNHp (5'-guanylylimidodiphosphate), the potassium current was gradually induced in the absence of agonists. As this current progressed, the magnitude of the glutamate- or kainate-evoked current transients became smaller and finally negligible. The GTP-gamma-S-induced current was not inhibited by argiopine. 8. These data indicate that in the molluscan neurones studied there are at least three pharmacologically distinct glutamate receptors: (1) a receptor of quisqualate-ibotenate type which directly controls chloride channel; (2) quisqualate and (3) kainate receptors which control in calcium-independent manner the common potassium channel by activation of GTP-binding protein.
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PMID:Different types of glutamate receptors in isolated and identified neurones of the mollusc Planorbarius corneus. 165 12

Activation of the respiratory burst in the monocytic cell line U937 by cross-linking human 40-kDa FcR for IgG (Fc gamma RII) with the IgG1 mAb, CIKM5, is dependent on the maturation state of the cell. Addition of anti-Fc gamma RII to undifferentiated cells does not activate the respiratory burst but differentiation with human rIFN-gamma (200 U/ml) for 13 to 15 days results in maximal stimulation by this agonist, with half-maximal responses in cells incubated for 10 to 12 days. During maturation the development of responsiveness to cross-linking Fc gamma RII occurs later than the development of responsiveness to the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (maximal responses at 7 to 9 days), or the chemotactic peptide FMLP (half-maximal responses at 7 to 9 days). The late development of maximal Fc gamma RII responses is not associated with either increased Fc gamma RII expression, enhanced calcium mobilization induced by anti-Fc gamma RII, changes in protein kinase C activity (PKC) or a switch in PKC isotype expression. Activation of the respiratory burst via Fc gamma RII may not be mediated by activation of PKC as the kinase inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride and N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride inhibited the Fc gamma RII response by less than 20% at concentrations which inhibit the 12-O-tetradecanoylphorbol-13-acetate-induced respiratory burst by more than 80%. IFN-gamma U937 cells did not metabolize incorporated arachidonate into eicosanoids when stimulated with anti-Fc gamma RII, suggesting that eicosanoids do not mediate activation of the respiratory burst, and this was confirmed by the lack of inhibition by the specific 5'-lipoxygenase and glutathione S-transferase inhibitor, piriprost, and the cyclo-oxygenase inhibitor, indomethacin. In addition there was no significant release of radiolabeled arachidonate in response to anti-Fc gamma RII. The response to anti-Fc gamma RII is inhibited by pertussis toxin, suggesting that signal transduction is via a GTP-binding protein. Agents that elevate intracellular cAMP increased the magnitude of the cAMP transients stimulated by anti-Fc gamma RII and also inhibited the respiratory burst. FMLP responses showed a similar pattern of sensitivity to this range of inhibitors, suggesting that both Fc gamma RII and FMLP receptor share common regulatory mechanisms. However, the termination of the respiratory burst activated via Fc gamma RII and FMLP receptor is independently regulated, in that after FMLP-induced activation there is no subsequent inhibition of the Fc gamma RII-mediated response and vice versa.
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PMID:Differentiation-linked activation of the respiratory burst in a monocytic cell line (U937) via Fc gamma RII. A study of activation pathways and their regulation. 165 5

Mouse neuroblastoma x rat glioma hybrid cells (N x G, 108CC15) were used to study the inhibitory effects of the synthetic opioid D-Ala2-D-Leu5-enkephalin (DADLE), somatostatin, adrenaline-alpha 2 and angiotensin II on voltage-dependent Ca(2+)-currents (ICa) using the patch-clamp technique in the whole-cell configuration mode. The inhibitory effects could be abolished by pretreatment of N x G cells with pertussis toxin or intracellular infusion of GDP beta S indicating an involvement of a pertussis toxin sensitive GTP-binding protein (G-protein), presumably Go. The effect of DADLE, the strongest inhibitor of ICa, was studied during dibutyryl cyclic AMP (dBcAMP) induced differentiation. Using omega-conotoxin GVIA (omega-CTX) and methoxyverapamil (D600) as specific Ca(2+)-channel blockers of the N- and L-type Ca(2+)-channels, it was found that in N x G cells DADLE predominantly induces inhibition of T- and N-type Ca(2+)-channels.
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PMID:Inhibitory modulation of fast and slow Ca(2+)-currents in neuroblastoma x glioma cells during differentiation. 165 35


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