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)

When stimulated, neutrophils undergo a complex change in cytoplasmic pH (pHi): an incipient acidification, followed by an alkalinization which is due to activation of Na+/H+ exchange. When the latter is inhibited by amiloride or by removal of extracellular Na+, the actual magnitude of the initial acidification can be fully appreciated. The acidification is thought to be of metabolic origin, but the precise origin of the H+ (equivalents) remains undefined. We used adenosine, a modulator of neutrophil responsiveness, to identify the source of metabolic acid in cells stimulated by either formylmethionylleucylphenylalanine (fMet-Leu-Phe) or 12-O-tetradecanoylphorbol 13-acetate (TPA). Pretreatment of the cells with adenosine inhibited the fMet-Leu-Phe-induced respiratory burst, but secretion of specific and azurophilic granules, as well as aggregation were unaffected. In fMet-Leu-Phe-treated cells, adenosine reduced the acidification recorded in Na+-free media, but had no effect on the activation of the Na+/H+ antiport. Adenosine had little or no effect on the TPA-induced responses, including the pHi changes. The respiratory burst, as well as the cytoplasmic acidification were also inhibited in parallel by pretreating the cells with 'islet-activating protein' from Bordetella pertussis. It was concluded that activation of the NADPH-oxidase and/or the associated stimulation of the hexose monophosphate shunt play a major role in the metabolic acidification of stimulated neutrophils.
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PMID:Cytoplasmic pH regulation in activated human neutrophils: effects of adenosine and pertussis toxin on Na+/H+ exchange and metabolic acidification. 302 27

The initial events in signal transduction in insulin-secreting cells are summarized in FIGURE 8. Both nutrient stimuli, such as glucose and amino acids and the muscarinic agonist carbachol (carbamylcholine) raise [Ca2+]i. Although the rise in [Ca2+]i precedes the stimulation of insulin release, it is not a moment-to-moment regulator of release. The metabolizable fuel stimuli cause Ca2+ influx through voltage-dependent Ca2+ channels following depolarization of the membrane potential. In contrast, carbachol, which does not depolarize, elicits Ptd Ins 4,5-P2 hydrolysis, a reaction catalyzed by phospholipase C. The generation of Ins 1,4,5-P3 in this instance is Ca2+ independent, but appears to involve a GTP-binding protein. However, this protein is not a substrate for pertussis toxin. The levels of Ins 1,4,5-P3, which releases Ca2+ from an ATP-dependent Ca2+ pool of the endoplasmic reticulum, are increased prior to the rise in [Ca2+]i. The mitochondria may take up Ca2+ after large increases in [Ca2+]i. A previously proposed second messenger, arachidonic acid, is much less selective than Ins 1,4,5-P3 in that it releases Ca2+ from mitochondria as well as from the endoplasmic reticulum in a slow and irreversible manner. As Ins 1,4,5-P3 is also generated during glucose stimulation of islets, albeit in a Ca2+-dependent manner, this metabolite could mediate not only the action of carbachol but also contribute to amplifying the [Ca2+]i rise in response to glucose.
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PMID:Signal transduction in insulin secretion: comparison between fuel stimuli and receptor agonists. 310 54

Addition of fibroblast growth factor to quiescent cultures of Swiss 3T3 cells stimulated the membrane transport of 2-deoxyglucose. Treatment of the cells with pertussis toxin (islet-activating protein) inhibited fibroblast growth factor-stimulated hexose transport. 5'-Guanylyl imidodiphosphate (p[NH]ppG), a non hydrolyzable analogue of GTP, increased the number of hexose carriers in the plasma membrane of saponin-permeabilized cells. These results suggest that guanine nucleotide binding protein may be involved in the regulation of hexose transport system by fibroblast growth factor in Swiss 3T3 cells.
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PMID:Inhibition by pertussis toxin of fibroblast growth factor-stimulated hexose transport in Swiss 3T3 cells. 311 8

A new assay method has been developed for the quantitative estimation of the inhibitory effect of pertussis vaccine on epinephrine-induced hyperglycaemia in mice. The statistical analysis of the assay was based on logarithm-transformed estimates of the blood glucose levels. The method was sufficiently sensitive to detect the activity of 0.004 millilitre of commercial combined diphtheria-tetanus-whole cell pertussis vaccine. The estimated common variance was as small as 0.0034 and the assay was highly reproducible. Among commercial vaccines there was a significant difference in activity. The activity of a stock pertussis vaccine was inactivated by 5 mM glutaraldehyde at 37 degrees C for 30 min, but resisted treatment with 40 mM formaldehyde at 37 degrees C for 5 days. The extent of inactivation with the chemicals was calculated by a parallel line assay as the activity relative to that of untreated control pertussis vaccine.
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PMID:Determination of the epinephrine-refractory hypoglycaemic activity of whole-cell pertussis vaccine in mice. 314 32

A toxoid vaccine, composed of purified pertussis toxin inactivated with H2O2 (NICHD-Ptxd), was developed on the basis of evidence that serum neutralizing antibodies (antitoxin) would confer immunity to pertussis. In vivo and in vitro assays of NICHD-Ptxd showed only trace or nondetectable levels of pyrogenic, adenosine diphosphate-ribosyltransferase, binding and pharmacologic activities. Nevertheless, about 40% of the antigenicity of pertussis toxin was retained. Adult volunteers were injected, two times 6 weeks apart, with either 10 (n = 21), 50 (n = 25), or 75 (n = 30) micrograms/dose of one lot, Ptx-06, adsorbed onto AI(OH)3. Neither fever nor changes in the levels of leukocytes, lymphocytes, fasting blood glucose, or insulin were observed in the volunteers. The optimal immunizing dose, 50 micrograms, induced levels of antitoxin (geometric mean (GM) 302 U) comparable to those found in eight adults convalescent from pertussis (GM 269 U) and greater than those found in 18-month-old children after their fourth dose of diphtheria and tetanus toxoids and pertussis vaccine (GM 20.0 U, p less than 0.001). These data indicate that NICHD-Ptxd is safe and immunogenic in adults, and they justify its evaluation in infants and children.
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PMID:Clinical, metabolic, and antibody responses of adult volunteers to an investigational vaccine composed of pertussis toxin inactivated by hydrogen peroxide. 326 85

Hypotonic-hyporesponsive episodes and persistent crying are specific complications of pertussis immunization. Hyperinsulinemia, hypoglycemia, and leukocytosis have been noted after pertussis vaccine administration in a murine model. Five children with hypotonic-hyporesponsive episodes and 6 children with persistent crying following DTP immunization were studied. The children were found to have leukocytosis acutely, similar to findings reported in children following routine DTP immunization. No abnormalities were noted in plasma insulin or serum glucose. Five of 6 children with persistent crying had severe local reactions, suggesting that localized inflammation may be a cause of persistent crying.
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PMID:An ongoing surveillance study of persistent crying and hypotonic-hyporesponsive episodes following routine DTP immunization: a preliminary report. 327 12

When rat pancreatic islets were incubated with 10(-8) M arginine vasopressin in the presence of 15 mM glucose there was a pronounced inhibition of insulin release in comparison with controls. This inhibitory effect appeared to be specific for vasopressin since it was antagonised by vasopressin antibody. Moreover, pertussis toxin (100 ng/ml) reversed the inhibition of insulin release due to vasopressin, indicating the possible involvement of a guanyl-nucleotide regulatory protein in the inhibitory effect. Nevertheless, 10(-8) M vasopressin increased islet concentrations of cyclic AMP even under conditions where insulin release was decreased.
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PMID:Pertussis toxin reverses the inhibition of insulin secretion caused by [Arg8]vasopressin in rat pancreatic islets. 328 20

The effects of pertussis toxin (PT) treatment on insulin-stimulated myristoyl-diacylglycerol (DAG) generation, hexose transport, and thymidine incorporation were studied in differentiated BC3H-1 myocytes. Insulin treatment caused a biphasic increase in myristoyl-DAG production which was abolished in myocytes treated with PT. There was no effect of PT treatment on basal (nonstimulated) myristoyl-DAG production. Insulin-stimulated hydrolysis of a membrane phosphatidylinositol glycan was blocked by PT treatment. ADP-ribosylation of BC3H-1 plasma membranes with [32P]NAD revealed a 40-kDa protein as the major PT substrate in vivo and in vitro. The time course and dose dependence of the effects of PT on diacylglycerol generation correlated with the in vivo ADP-ribosylation of the 40-kDa substrate. Pertussis toxin treatment resulted in a 71% attenuation of insulin-stimulated hexose uptake without effect on either basal or phorbol ester-stimulated uptake. The stimulatory effects of insulin and fetal calf serum on [3H]thymidine incorporation into quiescent myocytes were attenuated by 61 and 59%, respectively, when PT was added coincidently with the growth factors. Nonstimulated and EGF-stimulated [3H]thymidine incorporation was unaffected by PT treatment. These data suggest that a PT-sensitive G protein is involved in the cellular signaling mechanisms of insulin.
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PMID:Pertussis toxin treatment attenuates some effects of insulin in BC3H-1 murine myocytes. 328 21

Mice were infected intranasally with a sub-lethal dose of Bordetella pertussis organisms (1.2 x 10(5) colony forming units per mouse), control animals receiving the vehicle intranasally. The experiments were performed 14 days later. Serum glucose and insulin concentrations were studied across a 24 h period in freely fed animals and the changes in serum glucose and insulin concentrations in response to feeding were examined in mice fasted for 18 h. The responsiveness of mice to injected insulin (0.5 and 5.0 units/kg i.v.) was also examined. Pertussis-infected mice developed hypoglycaemia and hyperinsulinaemia relative to the controls. These changes were present across a 24 h period although the magnitude of the differences between values seen in control and infected animals varied and the hyperinsulinaemia was not seen at all times. Infected mice showed a markedly diminished hyperglycaemia and an exaggerated hyperinsulinaemia following food ingestion, relative to normal controls. Pertussis-induced hypoglycaemia was abolished following destruction of the pancreatic islet B cells with alloxan (80 mg/kg i.v.). The serum glucose response to a low dose of insulin was significantly attenuated by B. pertussis infection although the hypoglycaemia produced by a high dose was prolonged. It was concluded that B. pertussis infection-induced hypoglycaemia was secondary to hyperinsulinaemia, possibly caused by an exaggerated insulin secretory response to food intake.
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PMID:Role of insulin in the hypoglycaemic effect of sublethal Bordetella pertussis infection in mice. 351 82

Intranasal infection of mice with a sublethal dose of Bordetella pertussis produced hypoglycaemia and hyperinsulinaemia. Exposure to ether vapour did not modify serum insulin concentrations in control mice, but produced a marked transient hyperinsulinaemia in mice infected with B. pertussis. A similar hyperinsulinaemia in infected, but not control, mice was also seen after a brief (10-15 s) period of anoxia (produced by exposure to an atmosphere of 100% N2 or 100% CO2), or following the injection of histamine or 2-deoxyglucose. Exposure to cold (2-4 degrees C) or hypoxia (8% O2 in 92% N2), however, did not alter serum concentrations of insulin in control or infected mice. The hyperinsulinaemic response to ether stress observed in mice infected with B. pertussis was abolished by pretreatment with alloxan. The hyperglycaemic effects of histamine and 2-deoxyglucose were attenuated or abolished in mice infected with B. pertussis. However, none of the stimuli which produced hyperinsulinaemia in the infected mice resulted in any further lowering of the blood glucose concentration. Pretreatment of mice with pertussis toxin (150 ng/mouse, i.v.) produced hypoglycaemia similar in magnitude to that found in animals infected with B. pertussis. Moreover, exposure of mice treated with pertussis toxin to ether vapour produced marked hyperinsulinaemia. It is suggested that the metabolic alterations seen in animals infected with B. pertussis may be mediated by pertussis toxin.
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PMID:Hypoglycaemia and acute stress-induced hyperinsulinaemia in mice infected with Bordetella pertussis or treated with pertussis toxin. 354 69


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