UMLS:C0043167 - FACTA Search

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Query: UMLS:C0043167 (pertussis)
19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The noradrenalin-evoked production of [3H]inositol phosphates in mouse striatal astrocytes in primary culture appeared to be the result of the combined stimulation of alpha 1- and alpha 2-adrenergic receptors. Indeed, the noradrenalin (100 microM) response was only partially reproduced by a maximally effective concentration of methoxamine (100 microM), a selective agonist of alpha 1-adrenergic receptors. In addition, the noradrenalin (100 microM)-induced production of [3H]inositol phosphates, which was completely suppressed by the alpha 1-adrenergic antagonist prazosin (1 microM), was also partially inhibited by yohimbine, a selective antagonist of alpha 2-adrenoceptors (maximum inhibition = -57 +/- 11%, measured in the presence of 10 microM yohimbine; six experiments). Finally, UK14.304, a selective alpha 2-adrenergic agonist that was ineffective alone, enhanced the methoxamine-evoked production of [3H] inositol phosphates (EC50 = 86 +/- 21 nM; three experiments). These results suggest that the stimulation of alpha 1-adrenergic receptors is required for the alpha 2-adrenergic receptor-mediated enhancement of phospholipase C activity. The increased production of [3H]inositol phosphates resulting from the stimulation of alpha 2-adrenergic receptors involved pertussis toxin-sensitive G proteins (Gi/o) and depended on extracellular calcium. As shown using the fluorescent dye indo-1, noradrenalin (100 microM) induced a long-lasting increase in cytosolic calcium in striatal astrocytes. Moreover, noradrenalin (100 microM) stimulated [3H]arachidonic acid release from these cells. These two latter responses may result from synergistic effects due to the combined stimulation of alpha 1- and alpha 2-adrenergic receptors, because they were inhibited by either prazosin (1 microM) or yohimbine (10 microM). Finally, the noradrenalin-evoked production of [3H]inositol phosphates seems to result partly from an inhibition by arachidonic acid of glutamate uptake into astrocytes, leading to the stimulation of glutamate metabotropic receptors coupled to phospholipase C. Indeed, the alpha 2-adrenergic component of the noradrenalin response was suppressed by either enzymatic removal of external glutamate or addition of 2-amino-3-phosphonopropionic acid (1 mM), an antagonist of glutamate metabotropic receptors that blocked the glutamate-evoked production of [3H]inositol phosphates in striatal astrocytes, and was reproduced by the direct application of either glutamate or an inhibitor of glutamate uptake, beta-methyl-DL-aspartic acid.
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PMID:Role of arachidonic acid and glutamate in the formation of inositol phosphates induced by noradrenalin in striatal astrocytes. 790 16

Cholera toxin (CTX) is composed of two subunits, subunit A, which possesses ADP-ribosyltransferase activity, and subunit B, which is responsible for receptor binding. It has previously been shown that agents that increase cyclic AMP (cAMP) levels in cells induce differentiation of PC12 cells into neurite-like cells. In this report, we show that as little as 100 pg of CTX per ml induces such changes. CTX was found to ADP-ribosylate at least four membrane proteins of PC12 cells in vitro and in vivo and to increase intracellular cAMP levels. We have developed an inducible ctx gene expression system in Vibrio cholerae by using the tac promoter. The culture medium of the CTX-producing bacteria was able to induce the morphological changes and the ADP-ribosylation of the PC12 cell membrane proteins. We have constructed two CTX-cross-reactive mutant proteins (CTX-CRM) by site-directed mutagenesis. The choice of glutamic acid 29 as the target amino acid was based on sequence similarities with other bacterial toxins. CTX-CRM-E29 delta, in which the Glu-29 of the A subunit was deleted, showed strongly reduced ADP-ribosyltransferase activity and did not induce significant morphological changes of PC12 cells. In contrast, CTX-CRM-E29D, in which the Glu-29 was replaced by an aspartic acid, was as active as the wild-type protein. We conclude that the ADP-ribosylation activity of CTX is important for the toxin-induced differentiation of PC12 cells. Pertussis toxin, which had no visible effect on PC12 cell morphology, was also able to ADP-ribosylate a membrane-bound protein(s) in vitro and in vivo. Pertussis toxin alone did not significantly increase cAMP levels in PC12 cells, but it acted synergistically with CTX.
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PMID:Importance of ADP-ribosylation in the morphological changes of PC12 cells induced by cholera toxin. 792 73

The composition of the peptidoglycan of Haemophilus influenzae was determined by analyzing glycopeptides generated by M1 muramidase hydrolysis using high pressure liquid chromatography, fast atom bombardment mass spectrometry, and fast atom bombardment collisionally activated dissociation tandem mass spectrometry, and amino acid analysis. The structures of 17 glycopeptides, representing 96% of the total peptidoglycan, were ascertained. Fifteen glycopeptides resembled species described for Escherichia coli peptidoglycan (Glauner, B., and Schwarz, U. (1983) The Target of Penicillin (Hackenbeck, R., ed), Walter de Gruyter, Berlin pp. 29-34) as compared with 9 in common with Bordetella pertussis (Tuomanen, E., Schwartz, J., Sande, S., Light, K., and Gage, D. (1989) J. Biol. Chem. 264, 11093-11098). Substitutions for L-alanine in the fourth position of the stem peptide included glycine, aspartic acid, and serine. The peptidoglycan was 27% cross-linked, 2% of which formed between diaminopimelic acid residues. No species was identified containing lysyl-arginine residues characteristic of lipoprotein. The peptidoglycan of non-beta-lactamase-mediated antibiotic-resistant H. influenzae differed from that of sensitive strains by an increase in the amount of disaccharide tripeptides and a decrease in 1,6-anhydro dimers. Both changes were transformable properties that changed in a stepwise fashion in parallel with the degree of antibiotic resistance.
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PMID:Composition of the peptidoglycan of Haemophilus influenzae. 850 90

The effects of short deletions of the C terminus of the BvgA response regulator protein of the BvgAS two-component system were examined in Bordetella pertussis. When present as a single copy in the chromosome, deletions removing as few as two amino acids conferred a completely Bvg- phenotype. When provided in trans, on the broad-host-range plasmid pRK290, under the control of the native bvgAS promoter, deletions of two or three amino acids conferred a profound growth inhibition which was dependent on the integrity and activity of the wild-type chromosomal bvgAS locus. It is proposed that this phenotype was the result of an inappropriate interaction of the mutant BvgA protein with the RNA polymerase enzyme, specifically the alpha subunit. Mutant strains in which this growth inhibition was relieved were isolated and characterized. Although most of the suppressor mutations affected either the mutant plasmid copy or the wild-type chromosomal bvg locus, three mutations which affected the alpha subunit of B. pertussis RNA polymerase were also isolated. Two of these resulted in increased levels of the alpha subunit, and one caused a substitution of glycine for the aspartic acid residue at position 171, in the N-terminal domain. All three mutations also resulted in a differential phenotype in that expression of fha was essentially normal, but expression of ptx was greatly reduced.
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PMID:Mutations affecting the alpha subunit of Bordetella pertussis RNA polymerase suppress growth inhibition conferred by short C-terminal deletions of the response regulator BvgA. 957 2

Previous studies have indicated that stimulation of neuronal inhibitory receptors, such as the serotonin1A receptor (5-HT1A-R), could cause attenuation of the activity of both N-type Ca2+ channels and N-methyl-D-aspartic acid receptors, thus resulting in protection of neurons against excitotoxicity. The purpose of this study was to investigate if the 5-HT1A-R is also coupled to an alternative pathway that culminates in suppression of apoptosis even in cells that are deficient in Ca2+ channels. Using a hippocampal neuron-derived cell line (HN2-5) that is Ca2+ channel-deficient, we demonstrate here that an alternative pathway is responsible for 5-HT1A-R-mediated protection of these cells from anoxia-triggered apoptosis, assessed by deoxynucleotidyl-transferase-mediated dUTP nick end-labeling (TUNEL). The 5-HT1A-R agonist-evoked protection was eliminated in the presence of pertussis toxin and also required phosphorylation-mediated activation of mitogen-activated protein kinase (MAPK), as evidenced by the elimination of the agonist-elicited rescue of neuronal cells by the MAPK kinase inhibitor PD98059 but not by the phosphatidylinositol 3-kinase (PI-3K) inhibitor wortmannin. Furthermore, agonist stimulation of the 5-HT1A-R caused a 60% inhibition of anoxia-stimulated caspase 3-like activity in the HN2-5 cells, and this inhibition was abrogated by PD98059 but not by wortmannin. Although agonist stimulation of the 5-HT1A-R caused an activation of PI-3Kgamma in HN2-5 cells, our results showed that this PI-3Kgamma activity was not linked to the 5-HT1A-R-promoted regulation of caspase activity and suppression of apoptosis. Thus, in the neuronal HN2-5 cells, agonist binding to the 5-HT1A-R results in MAPK-mediated inhibition of a caspase 3-like enzyme and a 60-70% suppression of anoxia-induced apoptosis through a Ca2+ channel-independent pathway.
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PMID:Agonist stimulation of the serotonin1A receptor causes suppression of anoxia-induced apoptosis via mitogen-activated protein kinase in neuronal HN2-5 cells. 1009 53

delta-Opioid receptors belong to the superfamily of G protein-coupled receptors, characterized by seven putative transmembrane domains, and have been shown to interact with a host of effector systems. It has been suggested that the charge on the conserved aspartic acid residue at position 128 in transmembrane domain 3 of the delta-opioid receptor contributes to both the conformation of the receptor binding pocket and the molecular rearrangements which accompany the establishment of high-affinity states of the receptor. In light of this, we used site-directed mutagenesis to determine whether this residue participates in the transmission of signals to adenylyl cyclase, the effector with which opioid receptors have been classically associated. Substitution of this aspartic acid (D128) for the neutral amino acid alanine, or the protonated amino acids lysine and histidine, constitutively couples the receptor to adenylyl cyclase, as evidenced by a curtailed response to forskolin stimulation in transfected cells. In addition, this constitutive activity can be blocked by pretreatment of the transfected cells with pertussis toxin. Interestingly, naloxone blocks this effect in cells expressing the D128A mutant, but acts as an agonist at the D128K mutant. Our findings support the hypothesis that the interaction between agonist and receptor promotes conformational changes that may be mimicked, at least in part, by mutation of the aspartate residue at position 128. Furthermore, these changes appear to be involved not only in receptor activation, but also in the functional discrimination between agonists and antagonists.
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PMID:Altered adenylyl cyclase responsiveness subsequent to point mutations of Asp 128 in the third transmembrane domain of the delta-opioid receptor. 1047 67

The present study was designed to characterize the possible roles of spinally located cholera toxin (CTX)- and pertussis toxin (PTX)-sensitive G-proteins in excitatory amino acids induced pain response. Intrathecal (i.t.) injection of glutamate (20 microg), N-methyl-D-aspartic acid (NMDA; 60 ng), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA; 13 ng), and kainic acid (12 ng) showed pain response. Pretreatment with CTX (0.05 and 0.5 microg, i.t.) attenuated pain response induced by glutamate, NMDA, AMPA and kainic acid administered i.t. in a dose-dependent manner. On the other hand, i.t. pretreatment with PTX further increased the pain response induced by glutamate, NMDA, AMPA and kainic acid administered i.t., especially at the dose of 0.5 microg. Our results suggest that, at the spinal cord level, CTX- and PTX-sensitive G-proteins appear to play opposite roles in modulating the pain response induced by spinally administered. Furthermore, CTX- and PTX-sensitive G-proteins appear to modulate pain response induced by stimuli of both NMDA and non-NMDA glutamate receptors.
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PMID:Differential modulatory roles of cholera toxin and pertussis toxin in the regulation of pain responses induced by excitatory amino acids administered intrathecally in mice. 1083 21

The P2Y(2) nucleotide receptor (P2Y(2)R) contains the integrin-binding domain arginine-glycine-aspartic acid (RGD) in its first extracellular loop, raising the possibility that this G protein-coupled receptor interacts directly with an integrin. Binding of a peptide corresponding to the first extracellular loop of the P2Y(2)R to K562 erythroleukemia cells was inhibited by antibodies against alpha(V)beta(3)/beta(5) integrins and the integrin-associated thrombospondin receptor, CD47. Immunofluorescence of cells transfected with epitope-tagged P2Y(2)Rs indicated that alpha(V) integrins colocalized 10-fold better with the wild-type P2Y(2)R than with a mutant P2Y(2)R in which the RGD sequence was replaced with RGE. Compared with the wild-type P2Y(2)R, the RGE mutant required 1,000-fold higher agonist concentrations to phosphorylate focal adhesion kinase, activate extracellular signal-regulated kinases, and initiate the PLC-dependent mobilization of intracellular Ca(2+). Furthermore, an anti-alpha(V) integrin antibody partially inhibited these signaling events mediated by the wild-type P2Y(2)R. Pertussis toxin, an inhibitor of G(i/o) proteins, partially inhibited Ca(2+) mobilization mediated by the wild-type P2Y(2)R, but not by the RGE mutant, suggesting that the RGD sequence is required for P2Y(2)R-mediated activation of G(o), but not G(q). Since CD47 has been shown to associate directly with G(i/o) family proteins, these results suggest that interactions between P2Y(2)Rs, integrins, and CD47 may be important for coupling the P2Y(2)R to G(o).
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PMID:An RGD sequence in the P2Y(2) receptor interacts with alpha(V)beta(3) integrins and is required for G(o)-mediated signal transduction. 1133 1

Pertussis toxin of Bordetella pertussis is secreted by a type IV secretion system comprised of the products of the nine ptl (pertussis toxin liberation) genes. These proteins are believed to form a complex spanning both the inner and outer membranes and passing through the peptidoglycan layer. Peptidoglycan acts as a barrier for transport through the periplasm of large folded molecules. Assembled pertussis toxin and the secretion component proteins PtlC through PtlH are too large to diffuse through intact peptidoglycan. Therefore, we hypothesized that the Ptl system contains a peptidoglycanase activity. The PtlE protein was found to exhibit a sequence match to the active site of glycohydrolase enzymes. An N-terminally polyhistidine-tagged PtlE fusion protein, constructed and expressed in Escherichia coli and in B. pertussis, exhibited peptidoglycanase activity on activity gels. A fusion protein with alanine substitutions at the putative active site residues (aspartic acid at position 53 and glutamic acid at position 62) lacked peptidoglycanase activity. B. pertussis strains with the amino acid substitutions were deficient for pertussis toxin secretion. Based on these results, we concluded that PtlE is a peptidoglycanase responsible for the local removal or rearrangement of the peptidoglycan layer during Ptl secretion complex assembly.
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PMID:The PtlE protein of Bordetella pertussis has peptidoglycanase activity required for Ptl-mediated pertussis toxin secretion. 1200 25

The aim of the present study was to examine the effect of intrathecal (i.t.) injection of pertussis toxin (PTX) on the nociceptive threshold and protein kinase C (PKC) expression in the rat spinal cord. The role of N-methyl-D-aspartic acid (NMDA) receptors in these changes was also examined. Male Wistar rats were implanted with two i.t. catheters, one of which was connected to a mini-osmotic pump and used to infuse saline or D-2-amino-5-phosphonopentanoic acid (D-AP5) (2 microg/h) starting on day 3 after i.t. catheter insertion. Two days later, a single injection of saline or PTX (2 microg) was given via the other catheter, followed by a flush with 10 microl of saline. On day 4 after PTX or saline injection, the thermal paw withdrawal latency was measured, then the rats were sacrificed by decapitation, and the dorsal part of the lumbosacral spinal segments was removed for PKC Western blotting assays. In PTX-treated rats, thermal hyperalgesia was observed, and the PKCgamma content of both the synaptosomal membrane and cytosolic fractions was significantly increased. The levels of alpha-, betaI-, or betaII-PKC isozymes in these fractions were unaffected by PTX treatment. Infusion of the NMDA antagonist, D-AP5, prevented both the thermal hyperalgesia and the increase in PKCgamma isoform expression in PTX-treated rats, and had no effect on these values in nai;ve rats. Intrathecal injection of the PKC inhibitor, chelerythrine (10 microg), significantly inhibited the thermal hyperalgesia observed in PTX-treated rats. These results show that i.t. injection of PTX induced thermal hyperalgesia accompanied by a selective increase in PKCgamma expression in both the synaptosomal membrane and cytosolic fractions of the dorsal horn of the rat lumbar spinal cord, and both effects were inhibited by the NMDA receptor antagonist, D-AP5.
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PMID:D-2-amino-5-phosphonopentanoic acid inhibits intrathecal pertussis toxin-induced thermal hyperalgesia and protein kinase Cgamma up-regulation. 1256 Jan 6

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