Disease relevance of Whooping Cough

• Transgenic mice developed experimental allergic encephalomyelitis (EAE) following immunization with MBP and adjuvant plus pertussis toxin as well as with administration of pertussis toxin alone [1].
• Following administration of the MBP peptide, together with adjuvant and pertussis toxin, transgenic mice developed focal CNS inflammation and demyelination that led to clinical manifestations and disease courses resembling those seen in MS [2].
• Hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) by phospholipase C is mediated through coupling of surface receptors to a GTP-binding protein (Gp protein) which, in some cells, is inactivated by the toxin of Bordetella pertussis [3].
• Haemolysin is one of a family of membrane-targeted toxins, including the leukotoxins of Pasteurella and Actinobacillus and the bifunctional adenylate cyclase haemolysin of Bordetella pertussis, which require this protoxin activation 1-5 [4].
• Conversely, infection of 3T3-CCR5 cells can be inhibited by RANTES, anti-CCR5 polyclonal antibody, or herbimycin A but not by monoclonal antibodies that block HIV-1 infection or by pertussis toxin [5].

Psychiatry related information on Whooping Cough

• There were no significant differences in the immunolabeling of G alpha i1/2, G alpha q/11, or pertussis toxin-catalyzed [32P]ADP ribosylation in either tissue in the untreated bipolar affective disorder group compared with controls [6].
• By contrast, pertussis toxin had no effect on diphenhydramine- and scopolamine-induced amnesia [7].
• Experiments designed to gain insight into the muscarinic receptor subtypes mediating REM sleep enhancement involved pontine reticular formation administration of neostigmine after pertussis toxin, neostigmine after methoctramine, and neostigmine after pirenzepine [8].
• It is concluded that central administration of neuropeptide Y and sigma ligands abolish the stimulatory effects of psychological stress on caeco-colonic motility by blocking the pathways by which CRF activates the motility, through a common mechanism involving a pertussis toxin-sensitive Gi protein [9].

High impact information on Whooping Cough

• Two different G proteins coupled to the melatonin receptors have been described, one sensitive to pertussis toxin and the other sensitive to cholera toxin [10].
• D2 or adenosine A2 receptor blockade, pertussis toxin, Rp-cAMPS, or overexpression of dominant-negative peptides that sequester betagamma dimers prevent synergy [11].
• The receptor, now termed CX3CR1, requires pertussis toxin-sensitive G protein signaling to induce migration but not to support adhesion, which also occurs without other adhesion molecules but requires the architecture of a chemokine domain atop the mucin stalk [12].
• The acellular DTP vaccine was either one containing filamentous hemagglutinin, pertactin, and pertussis toxin inactivated with formalin and glutaraldehyde (SmithKline Beecham) or one with filamentous hemagglutinin, pertactin, and genetically detoxified pertussis toxin (Chiron Biocine) [13].
• Our data suggest that the mitogenic action of LPA occurs through Gi or a related pertussis toxin substrate and that the phosphoinositide hydrolysis-protein kinase C pathway is neither required nor sufficient, by itself, for mitogenesis [14].

Chemical compound and disease context of Whooping Cough

• Inhibition of receptor-mediated release of arachidonic acid by pertussis toxin [15].
• A similar apparent anomaly is seen with pertussis toxin, which has been shown to inhibit the Gi subunit of adenylate cyclase, and has a greater effect on cAMP accumulation and lipolysis than the activation by cholera toxin of the Gs subunit [16].
• In the absence of intracellular Ca2+ and Na+, AMPA, but not NMDA, brought about changes in a guanine-nucleotide-binding protein (Galpha[il]) that inhibited pertussis toxin-mediated ADP-ribosylation of the protein in an in vitro assay [17].
• Endothelin-1, but not endothelin-3, inhibited the L-type calcium current by decreasing cyclic AMP accumulation and activated the muscarinic potassium current by stimulating a pertussis toxin-sensitive GTP-binding protein [18].
• In contrast, m3 receptors potently activate phosphatidyl inositol hydrolysis and stimulate large, rapid and transient chloride currents by a pertussis toxin-insensitive G protein pathway [19].

Biological context of Whooping Cough

• The apoptotic cell death induced by PS2 protein was sensitive to pertussis toxin, suggesting that heterotrimeric GTP-binding proteins are involved [20].
• Neither PKC down-regulation by TPA nor inhibition of Gi proteins by pertussis toxin pretreatment influences CSF-1-induced signaling to TCFs [21].
• SDF-1-induced chemotaxis is inhibited by pertussis toxin, suggesting that its signaling in CD34+ cells is mediated by seven transmembrane receptors coupled to Gi proteins [22].
• MHC-restricted recognition of immunogenic T cell epitopes of pertussis toxin reveals determinants in man distinct from the ADP-ribosylase active site [23].
• Activation of c-fos gene expression by FMLP is mediated through a pertussis toxin-sensitive G protein, since pertussis toxin treatment of the cells blocked the induction of the c-fos gene by FMLP but not PMA [24].

Anatomical context of Whooping Cough

• Treatment of guinea pig neutrophils with pertussis toxin (islet-activating protein; IAP) results in inhibition of N-formyl peptide receptor-mediated release of arachidonic acid and granular enzymes [15].
• One class including epidermal growth factor, platelet derived growth factor and fibroblast growth factor activates receptor tyrosine kinases, and the second class, including thrombin, bombesin, bradykinin and vasopressin activates a phosphoinositide-specific phospholipase C through GTP-binding proteins which can be inactivated by pertussis toxin [25].
• Potassium channels in isolated, inside-out patches of membranes from atrial cells now are shown to be activated by a purified pertussis toxin-sensitive G protein of subunit composition alpha beta gamma, with an alpha subunit of 40,000 daltons [26].
• A 41-kilodalton protein from myocytes cultured with sympathetic neurons and from adult rat myocardium showed, respectively, 2.2- and 16-fold increases in pertussis toxin-associated ADP-ribosylation (ADP, adenosine diphosphate) as compared to controls [27].
• Thus, studies using transfected cells and cell-free systems show that a pertussis toxin-sensitive trimeric G protein, G(i3), is involved in the formation of secretory vesicles from the Golgi complex [28].

Gene context of Whooping Cough

• RXFP2 activates adenylate cyclase in recombinant systems, but physiological responses are sensitive to pertussis toxin [29].
• The MK chemotaxis induced by SDF-1 was inhibited by the CXCR4-specific mAb (12G5) and by pertussis toxin, demonstrating that signaling via the G protein-coupled receptor CXCR4 was necessary for migration [30].
• Signaling from both CCR5 and CXCR4 is mediated by pertussis toxin (PTX)-sensitive G(i) proteins and is not required for HIV-1 entry [31].
• In contrast, pertussis toxin-sensitive B cell sticking does not require SLC or MIP-3beta signaling, and occurs efficiently in SLC(low/-) HEV segments in wild-type mice, and in the SLC-negative HEVs of DDD/1 mice [32].
• Finally, expression of mutated forms of p21 ras did not abrogate the sensitivity of phospholipase C activation to pertussis toxin [33].

Analytical, diagnostic and therapeutic context of Whooping Cough

• Migration efficacy and Bordetella pertussis toxin-sensitive Ca(2+) mobilization responses to BRAK were strongly enhanced after treatment of monocytes with the cyclic AMP-elevating agents prostaglandin E(2) and forskolin [34].
• 64 healthy infants 2-3 months old, were randomly assigned to one of three vaccination groups which received either diphtheria-pertussis-tetanus (DPT) vaccine, Haemophilus influenzae type b capsular polysaccharide polyribosyl-ribitol phosphate (PRP) vaccine, or PRP + P (with pertussis adjuvant) vaccine in three doses at intervals of 2 months [35].
• Efficacy of salbutamol in treatment of infant pertussis demonstrated by sound spectrum analysis [36].
• Site-directed mutagenesis of four residues in B. pertussis adenylate cyclase situated in the second (Asp188, Asp190) and third (His298, Glu301) segments of identity were accompanied by important decrease, or total loss, of enzyme activity [37].
• Dissection of thymocyte signaling pathways by in vivo expression of pertussis toxin ADP-ribosyltransferase [38].

References