Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nature of the pathogenesis and of the prolonged immunity of whooping cough has not been clearly defined. The literature of Bordetella pertussis indicated that only the antigen that induces histamine sensitization, lymphocytosis, and other biological reactions in mice is the cause of the harmful effects and prolonged immunity of whooping cough. This antigen has the general characteristics of bacterial protein exotoxins that cause the harmful effects of infectious diseases such as diphtheria and tetanus. It is proposed that this antigen, which is histamine-sensitizing, lymphocyte-leukocyte-promoting, and islets-activating (HSF-LPF-IAP), be designated pertussis toxin. Agglutinogen, hemagglutinin, and heat-labile (at 56 C) and heat-stable (at 100 C) toxins are no doubt interrelated with the immunologic and/or toxic reactions of whooping cough. It appears that the first defense against the disease is the antibody that prevents adhesion of the bacteria to the cilia of the respiratory epithelium and that the second defense is the antitoxin against pertussis toxin (HSF-LPF-IAP).
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PMID:Pertussis toxin: the cause of the harmful effects and prolonged immunity of whooping cough. A hypothesis. 23 66

The signal transduction of prostaglandin E2 (PGE2) and thromboxane A2 (TXA2), cyclooxygenase products of arachidonic acid, was investigated in smooth muscle preparations and 1321N1 human astrocytoma cells. While PGE2 has been known to stimulate (via EP2 receptor) or inhibit (via EP3 receptor) adenylate cyclase, PGE2 activated phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phospholipase C (PLase C) in non-vascular smooth muscles (via EP1 receptor), resulting in accumulations of inositol trisphosphate (IP3) and diacylglycerol to elicit intracellular Ca2+ mobilization. On the other hand, STA2, a TXA2 receptor analogue, also accumulated IP3 in human astrocytoma cells. [3H]SQ 29548, a TXA2 receptor antagonist, specifically bound to astrocytoma membranes. TXA2-receptor antagonists (ONO NT-126, S-145, SQ29548 and ONO3708) concentration-dependently inhibited PIP2-specific PLase C activation by STA2, and they also inhibited [3H]SQ 29548 binding in human astrocytoma cells. The Ki value of each antagonist in PIP2-specific PLase C inhibition was similar to that in [3H]SQ29548 binding inhibition. In membrane preparations, STA2 activated PIP2-specific PLase C in the presence of GTP gamma S. Pertussis toxin (IAP) did not affect STA2-induced PLase C activation. The results suggest that stimulation of TXA2 receptors activates PIP2-specific PLase C via an IAP-insensitive G-protein.
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PMID:[Signal transduction of prostaglandin E2 and thromboxane A2]. 131 76

The mechanisms of action of lithium and antidepressants were investigated with reference to effects of these drugs on monoaminergic receptors and receptor-coupled adenylate cyclase systems in rat brain. Oral administration of lithium carbonate for 21 days decreased significantly the density of beta-adrenergic receptors in rat cerebral cortex, which is the same change as reported as the result of long-term treatment with many antidepressants. With regard to 5-hydroxytryptamine (5-HT) receptor subtypes, lithium treatment reduced the maximum number of 5-HT1A receptors in rat hippocampus but not in cerebral cortex, whereas repetitive injections with imipramine or desipramine did not. beta-Adrenoceptor-coupled adenylate cyclase activity was subsensitized by long-term lithium treatment in consistency with above-mentioned down-regulation of beta-adrenergic receptors. Stimulation of adenylate cyclase activity by non-hydrolyzable GTP analogue, guanyl-5'-ylimidodiphosphate (Gpp(NH)p), was, however, unaltered in lithium-treated rats as compared with controls. On the other hand, 5-HT1A-mediated inhibition of forskolin-stimulated adenylate cyclase in rat hippocampal membranes was not altered by chronic treatment with lithium or antidepressants. Gpp(NH)p-induced inhibition of forskolin-stimulated adenylate cyclase activity was not influenced by lithium treatment, either. [3H]Forskolin binding to rat cerebral cortex, which is assumed to be associated with the activated complex of catalytic subunit of adenylate cyclase and stimulatory guanine nucleotide-binding regulatory proteins (Gs), was not changed by administration of lithium or antidepressants under any condition studied. Pertussis toxin (islet-activating protein, IAP) sensitive G proteins (Gi/Go) as determined by using IAP-catalyzed [32P]ADP-ribosylation was not altered by lithium- or antidepressant-treatment, either. The implication of these results is discussed with a view of clarifying the mechanisms of action of these thymoleptic drugs.
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PMID:[Effects of lithium and antidepressants on monoaminergic receptors and receptor-coupled adenylate cyclase system in rat brain]. 131 19

We examine the autocrine activity of glycosyl inositol phosphate (InP-gly) on thyroid metabolism. The cAMP accumulation promoted by thyrotropin (TSH) or forskolin was modulated by InP-gly, stimulated by the lowest tested concentration (10(-8) M) and progressively inhibited by higher concentrations. Iodide uptake and iodine organification were decreased in a concentration-dependent manner by InP-gly alone, or in the presence of TSH. The IAP component of pertussis toxin blocked the inhibitory action of InP-gly on cAMP accumulation by reconstituted thyroid follicles (RTF), suggesting the participation of Gi protein. But the same treatment with IAP was without effect on iodine metabolism, suggesting that there is a second target for InP-gly, more distal than Gi protein, or coupled to another G protein which is insensitive to the toxin.
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PMID:Autocrine biological effects of glycosyl inositol phosphate produced by reconstituted pig thyroid follicles: role of pertussis toxin sensitive G proteins. 131 25

In rabbit peritoneal neutrophils prelabeled with [3H] lyso platelet-activating factor, a protein kinase C inhibitor, staurosporine (> 1 microM), increased [3H]phosphatidylethanol ([3H]PEt) level in the presence of ethanol in a concentration- and time-dependent manner, providing evidence for staurosporine activation of phospholipase D (PLD). The staurosporine activation of the enzyme absolutely required both extracellular calcium and cytochalasin B, and was almost completely inhibited by pretreatment of the cells with pertussis toxin (IAP). In a reconstituted system where the purified Gi1 had been incorporated into phospholipid vesicles, staurosporine activated GTPase activity of Gi1 in a concentration-dependent fashion, with a maximal 4-5-fold effect. ADP-ribosylation by IAP of Gi1 in vesicles significantly suppressed the staurosporine activation. As with the GTPase activity of Gi1, GTPase activities of other purified IAP-sensitive G proteins, such as Gi2 and G(o), were significantly stimulated by staurosporine, but the cholera toxin substrate Gs was appreciably less sensitive to the staurosporine stimulation. The staurosporine activation of GTPase was also observed in rabbit neutrophil membranes from control cells, but not in membranes from IAP-treated neutrophils. From these results, we conclude that the staurosporine activation of PLD in rabbit neutrophils is attributed to the direct activation of an IAP-sensitive G protein in a similar manner to receptors occupied by agonists. By contrast, staurosporine failed to activate phosphoinositide-specific phospholipase C (PI-PLC) under the conditions in which it activated PLD, indicating that there exists a PLD activation pathway independent of PI-PLC. Furthermore, it was found that N-acetyl-beta-glucosaminidase release from the granules of intact neutrophils was evoked by staurosporine to almost the same extent as by fMLP (100 nM), but O2- generation was not affected. These results suggest a possibility that PLD pathway plays an important role in enzyme release, but is not sufficient for O2- generation, in rabbit peritoneal neutrophils.
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PMID:A protein kinase C inhibitor, staurosporine, activates phospholipase D via a pertussis toxin-sensitive GTP-binding protein in rabbit peritoneal neutrophils. 133 Oct 88

Adenylate cyclase activity was measured on membrane fractions from the gill epithelium of rainbow trout Salmo gairdneri. Basal and glucagon-stimulated activities responded negatively to homologous neurohypophyseal peptides (arginine-vasotocin and isotocin). This inhibitory effect was totally abolished in the presence of pertussis toxin (IAP). The guanine nucleotide dependence of the enzyme was further explored by using GTP, GDP, and their stable analogs Gpp(NH)p, GTP gamma S, and GDP beta S. The results suggest that neurohypophyseal peptides at low concentrations inhibit the adenylate cyclase system directly by way of a Gi-protein, thus implying the intervention of a new type of membrane receptor for these hormones in fish gills.
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PMID:Gi protein mediates adenylate cyclase inhibition by neurohypophyseal hormones in fish gill. 148 May 12

1. A possible coupling of the rat cerebral cortex 5-hydroxytryptamine (5HT)-1A receptors to isletactivating protein (IAP, pertussis toxin) sensitive Gi protein was investigated by studying the effects of a guanosine 5'-triphosphate (GTP) and IAP injection to the rat ventricle. 2. Scatchard analysis showed that Bmax value of the high-affinity componentin [3H]8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) binding was decreased by pretreatment with IAP. 3. GTP caused a significant decreased Bmax of the high affinity site for [3H]8-OH-DPAT binding. It was noted that the IAP suppressed the cyclic AMP production by 5HT, VIP and Forskolin. 4. These results suggest that the rat cortex 5HT-1A receptors are linked to the Gi protein. 5. After 3 weeks chronic administration of amitriptyline (5mg/kg), desipramine (5mg/kg), imipramine (5mg/kg), doxepin (5mg/kg) and trazodone (10mg/kg), the receptor binding assay was carried out on 5HT-1A receptors. 6. It was observed that all the antidepressant drugs except for imipramine increased the number of high-affinity sites of the 5HT-1A receptors in the frontal cortex. 7. These results suggested that the increase of the Bmax for the 5HT-1A receptor might be related to the effectiveness of the antidepressant drugs.
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PMID:Effect of IAP and chronic antidepressant administration on the 5HT1A receptor in rat cortical membranes. 158 91

The optimum condition to quantitate the [32P]ADP-ribosylation catalyzed by pertussis toxin (islet-activating protein, IAP) in human platelet membranes was investigated. Autoradiography indicated the incorporation of 32P into the band corresponding to the molecular weight of 40-41 kDa, which was augmented by the addition of GTP in the presence of 10 mM MgCl2. On the other hand, non-hydrolyzable GTP analogue, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) enhanced the IAP-catalyzed [32P]ADP-ribosylation only in the absence of MgCl2. The amounts of IAP-catalyzed [32P]ADP-ribosylation in the presence of 100 microM GTP and 10 mM MgCl2 were linear in proportion to the protein concentrations within the limited range of protein concentrations, indicating that this simple quantitative method could be adequately used to evaluate the IAP-sensitive G proteins. Data from fifteen healthy volunteers (7 males and 8 females ranging 24 to 60 years old) indicate that the amounts of IAP-sensitive G proteins in platelet membranes are significantly negatively correlated with ages.
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PMID:Quantitative determination of pertussis toxin-sensitive G proteins using [32P]ADP-ribosylation in human platelet membranes: negative correlation with ages. 159 71

Addition of lithium ion to the inhibitory GTP-binding (Gi) protein resulted in a decrease of its ADP-ribosylation by islet-activating protein (pertussis toxin, IAP). The possibility that this decrease was due to dissociation of the Gi protein trimer was examined. Results showed that lithium ions had no appreciable effect on either the Gi protein trimer or its dissociation into its three subunits induced by Mg2+ and GTP gamma S. Next, the effect of lithium ions on Gi protein-mediated adenylate cyclase inhibition and alpha 2-adrenoceptor in human platelet membranes was examined. Lithium ion was found to impair adenylate cyclase inhibition of alpha 2-adrenoceptor stimulation of forskolin-stimulated enzyme activities. The monovalent ion also abolished guanine nucleotide modulation (GTP shift) of agonist binding, while it had no remarkable effects on antagonist binding in alpha 2-adrenoceptor of human platelet membranes. These results suggested that lithium ion caused functional change of the Gi protein without remarkable change of its dissociation, causing modulation in a coupling between alpha 2-adrenoceptor and Gi protein.
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PMID:Effects of lithium ion on the inhibitory GTP-binding protein and its coupling response. 164 75

Exposure of pig epidermis to adenylate cyclase stimulators results in receptor-specific desensitization. We investigated the nature of the agonist-induced desensitization, which was compared with the phorbol ester-induced, receptor-nonspecific desensitization. Both phorbol ester-induced desensitization and the agonist-induced desensitization were accompanied by an increase in forskolin- and cholera toxin-induced cyclic AMP accumulations. The magnitude of the increase in the agonist-induced desensitization was parallel to the degree of the initial cyclic AMP accumulation; histamine and adenosine, which increase more cyclic AMP than epinephrine, resulted in a more marked increase in forskolin- and cholera toxin-induced cyclic AMP accumulations. Similarly, epidermis desensitized to multiple receptors revealed more marked forskolin- and cholera toxin-induced cyclic AMP accumulations than epidermis desensitized to a single receptor. In contrast to the phorbol ester-induced desensitization, agonist-induced desensitization was not affected by the protein kinase C inhibitors H-7 and staurosporin. Further, agonist-induced desensitization was still inducible in phorbol ester-desensitized epidermis and vice versa. In contrast to the agonist-induced desensitization, which is accompanied by the preceding adenylate cyclase stimulation, no evidence for the stimulation of the adenylate cyclase during phorbol ester treatment was obtained. Neither agonist-induced desensitization nor phorbol ester-induced desensitization affected the content of inhibitory guanine nucleotide binding protein of the epidermis, which was monitored by the pertussis toxin (IAP)-catalyzed ADP ribosylation reaction. Our results indicate that agonist-induced desensitization and the phorbol ester-induced desensitization are independent of each other. Although both processes are characterized by increased forskolin- and toxin-induced cyclic AMP accumulations, the former is accompanied by initial cyclic AMP accumulation; the latter is not.
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PMID:Desensitization of the epidermal adenylate cyclase system: agonists and phorbol esters desensitize by independent mechanisms. 164 51


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