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)

Extracellular ATP plays an important role in the regulation of prostacyclin and nitric oxide release from vascular endothelial cells. These cellular responses to ATP are generally attributed to the stimulation of the P2y subtype of P2 purinergic receptors. However, it has recently been suggested that two types of ATP receptors might coexist on endothelial cells. To evaluate this hypothesis, we examined the effects of P2y receptor agonists 2-methylthioadenosine 5'-triphosphate (2MeSATP) and 2'- and 3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (BzATP) and of UTP on the accumulation of inositol phosphates in bovine aortic endothelial cells. BzATP, 2MeSATP, and UTP produced a smaller maximal effect than ATP. The effects of 2MeSATP and UTP were additive, whereas the effects of ATP and either UTP or 2MeSATP were not. Prior exposure to UTP reduced the subsequent response to UTP to 12% of the control response, whereas the response to 2MeSATP was decreased to 61%. Reciprocally, preincubation with 2MeSATP reduced the subsequent response to 2MeSATP to 23% of the control response, whereas the response to UTP was reduced to 73%. Pertussis toxin pretreatment decreased the response to both ATP and UTP (65% and 70% inhibition, respectively), whereas the response to 2MeSATP was not modified. Our data support the hypothesis that two classes of receptors recognizing ATP are expressed on bovine aortic endothelial cells.
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PMID:Heterogeneity of ATP receptors in aortic endothelial cells. Involvement of P2y and P2u receptors in inositol phosphate response. 843 80

Certain endothelial receptors are coupled to a pertussis toxin-sensitive inhibitory guanine nucleotide-binding regulatory (Gi) protein. In pigs, hypercholesterolemia causes a selective impairment of this Gi protein-dependent pathway. Recent studies have suggested that hypercholesterolemia-induced endothelial dysfunction may be caused by lysophosphatidylcholine (LPC) derived from oxidized low-density lipoprotein (LDL). The aim of the present study was to determine whether LPC could inhibit the Gi protein-dependent pathway. Isolated rings of porcine coronary arteries were suspended for isometric tension recording in organ chambers filled with physiological salt solution (37 degrees C, 95% O2-5% CO2). In rings with endothelium contracted with prostaglandin F2 alpha, pertussis toxin (100 ng/ml) or LPC (10(-5) M) inhibited the endothelium-dependent relaxations evoked by UK-14,304, an alpha 2-adrenergic agonist, or by serotonin, but not those caused by bradykinin or ADP. LPC also did not inhibit relaxations produced by SIN 1, an endothelium-derived relaxing factor-nitric oxide donor. After treatment of the rings with pertussis toxin, LPC no longer inhibited the endothelium-dependent relaxations to serotonin. Although LPC inhibited the responses of membrane-bound receptors that activate the pertussis toxin-sensitive Gi protein, LPC did not affect the endothelium-dependent relaxations evoked by direct activation of the pertussis toxin-sensitive Gi protein by fluoride. These results suggest that LPC selectively inhibits a Gi protein-dependent pathway in porcine endothelial cells possibly by disrupting receptor-G protein interactions. LPC that is associated with oxidized LDL may mediate in part the dysfunction in the endothelial Gi protein-dependent pathway associated with hypercholesterolemia.
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PMID:Lysophosphatidylcholine modifies G protein-dependent signaling in porcine endothelial cells. 845 75

During endotoxin shock macrophages produce arachidonic acid (AA) metabolites, nitric oxide (NO) and interleukin 6 (IL-6). In contrast, macrophages from endotoxin tolerant rats become hyporesponsive to LPS-induced AA metabolites production. However the role of NO and IL-6 during endotoxin tolerance is not known. Therefore, we evaluated the production of the AA metabolite 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), IL-6 and NO (by nitrite measurement) by peritoneal macrophages from endotoxin tolerant rats. Since pertussis toxin (PT) sensitive guanine nucleotide binding regulatory (Gi) protein activity is altered during endotoxin tolerance, we also studied the effect of PT on the regulation of the above mediators synthesis. Endotoxin tolerance was induced in rats by intraperitoneal injection of a sublethal dose of Salmonella enteritidis lipopolysaccharide (LPS, 100 micrograms/kg ip). Peritoneal macrophages were harvested 24 hours after LPS injection and stimulated in vitro with LPS (50 micrograms/ml) for determination of NO activity by nitrite, 6-keto-PGF1 alpha and IL-6 production. In macrophages collected from vehicle-pretreated rats (control) LPS stimulates all three mediators. In vivo pretreatment with LPS induced a desensitization of macrophages to LPS-induced 6-keto-PGF1 alpha production compared to control macrophages (p < 0.001). LPS-stimulated IL-6 synthesis was also partially, but not completely, reduced in tolerant macrophages (p < 0.001 versus control).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reorientation of macrophage mediator production in endotoxin tolerance. 852 61

Previous studies have shown that the neuropeptide, eclosion hormone, stimulates a nitric oxide-independent increase in the levels of cGMP in the nervous system of Manduca sexta. By contrast, recent results in Bombyx mori suggest that eclosion hormone increases cGMP via the production of nitric oxide. In view of these conflicting results we have carried out additional studies to test whether nitric oxide is involved in this process in Manduca. Evidence presented here supports our earlier observations that in Manduca the eclosion hormone-stimulated increase in cGMP is nitric oxide- and carbon monoxide-independent. In addition, we show that a wide variety of inhibitors of lipid metabolism block the eclosion hormone-stimulated cGMP increase. This supports the hypothesis that the activation of the guanylate cyclase is mediated by a lipid messenger. We also show that eclosion hormone stimulates an increase in the levels of inositol(1,4,5)trisphosphate. The time-course of this increase is consistent with the hypothesis that eclosion hormone stimulation of a phospholipase C is an early event in the cascade that results in an increase in cGMP. Receptor-mediated lipid hydrolysis is often mediated by G protein-coupled receptors. Experiments using pertussis toxin show that the eclosion hormone-stimulated increase in cGMP is not mediated by a pertussis toxin-sensitive G protein.
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PMID:Eclosion hormone-stimulated cGMP levels in the central nervous system of Manduca sexta: inhibition by lipid metabolism blockers, increase in inositol(1,4,5)trisphosphate and further evidence against the involvement of nitric oxide. 857 54

We examined the major pathogenic substances of Bordetella pertussis for the ability to induce nitric oxide, and important biological function of macrophages, via gamma interferon in spleen cells. B. pertussis, which produces a variety of pathogenic substances, including pertussis toxin and filamentous hemagglutinin, causes a severe respiratory disease. Nitric oxide was detected in the culture fluid of spleen cells stimulated with pertussis toxin or its B oligomer but not in the culture fluid of spleen cells stimulated with the A protomer of pertussis toxin or with filamentous hemagglutinin. Incubation of the peritoneal exudate macrophages with pertussis toxin, B oligomer, A protomer, or filamentous hemagglutinin induced little nitric oxide, whereas incubation with gamma interferon induced a significant amount of nitric oxide. The induction of nitric oxide in spleen cells stimulated with pertussis toxin was completely inhibited by anti-gamma interferon antibody. The treatment of spleen cells with anti-Thy-1.2 antibody plus complement followed by stimulation with pertussis toxin decreased the secretion of gamma interferon and nitric oxide. These results suggest that gamma interferon from T lymphocytes stimulated with pertussis toxin induces nitric oxide.
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PMID:Nitric oxide induction by pertussis toxin in mouse spleen cells via gamma interferon. 860 94

The effect of human parathyroid hormone-related protein, a powerful vasodilator, on endothelin-1 production in cultured bovine pulmonary arterial endothelial cells was studied. Treatment with parathyroid hormone-related protein(1-34) at concentrations of 10(-9) to 10(-6) mol/L for 24 hours caused dose-dependent suppression of the secretion of endothelin-1, with maximal suppression at 10(-7) mol/L to 74% of the control value. This inhibitory effect was completely abolished by coincubation with 100 ng/mL pertussis toxin, an inhibitor of GTP binding protein. Furthermore, addition of Ng-monomethyl-L-arginine, an inhibitor of nitric oxide synthase, at 10(-3) mol/L significantly blocked the suppressive effect of parathyroid hormone-related protein (1-34) on endothelin-1 secretion, and further addition of 5x10(-3) mol/L L-arginine significantly attenuated the blocking effect of N(G)-monomethyl-L-arginine. Parathyroid hormone-related protein (1-34) at 10(-7) mol/L resulted in an approximately fivefold increase in intracellular cGMP level. Northern blot analysis revealed that parathyroid hormone-related protein (1-34) inhibited both basal and thrombin-induced endothelin-1 gene expression. These findings suggest that the vasodilating property of parathyroid hormone-related protein may be mediated in part through its inhibitory effect on endothelin-1 production, which is probably mediated through nitric oxide and cGMP in endothelial cells. Thus, a feedback regulatory mechanism may exist between parathyroid hormone-related protein and endothelin-1 in the vascular wall.
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PMID:Parathyroid hormone-related protein inhibits indothelin-1 production. 869 38

Nitric oxide (NO) exhibits potent antimicrobial activity in vitro. The function of NO in host defenses in vivo, however, is presently unclear. Experiments were undertaken to determine the production of NO in vitro from murine peritoneal and alveolar macrophages, and murine macrophage cell line (J774A.1) stimulated with Bordetella pertussis or pertussis toxin (PT). In addition, we determined circulating levels of NO in the sera and bronchoalveolar lavage (BAL) fluids of mice infected intranasally with B. pertussis. The results of this study showed that in vitro murine peritoneal macrophages induce production of NO in response to B. pertussis and PT. In addition, murine macrophage cell line, J774A.1 also induces NO production after stimulation with B. pertussis. NO production was also detected in alveolar macrophages from mice infected intranasally with B. pertussis. Finally, a significant increment of circulating levels of NO was noted, in the sera but not in the BAL fluids, of mice infected intranasally with B. pertussis.
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PMID:In vitro and in vivo induction of nitric oxide by murine macrophages stimulated with Bordetella pertussis. 873 Oct 16

The effects of sodium orthovanadate, an inhibitor of protein tyrosine phosphatases, on the endothelial nitric oxide (NO) pathway were studied in vitro. Vanadate caused endothelium-dependent relaxations in isolated porcine coronary arteries, which were abolished by N omega-nitro-L-arginine methyl ester. The relaxations were also abolished by pertussis toxin, an inhibitor of certain G proteins. Tyrosine kinase inhibitors, genistein and alpha-cyano-3-ethoxy-4-hydroxy-5-phenyl-methylcinnamamide (ST-638), significantly attenuated the vanadate-induced relaxations. Vanadate also caused pertussis toxin-sensitive, endothelium-dependent relaxations in isolated porcine renal and femoral arteries and jugular veins. Immunoblots, using an antibody to phosphotyrosines and to c-Src in native porcine aortic endothelial cells, respectively, showed that vanadate induced an elevation of phosphotyrosine proteins and a decrease in the amount of the active form of c-Src family kinases; both changes were markedly suppressed by cotreatment with ST-638. These results indicate that in porcine blood vessels, vanadate causes a synthesis of endothelium-derived NO for which endothelial tyrosine kinases and pertussis toxin-sensitive G protein are considered to be closely involved.
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PMID:Vanadate causes synthesis of endothelium-derived NO via pertussis toxin-sensitive G protein in pigs. 876 Jan 88

Though nitric oxide (NO) plays a role in many normal pulmonary functions and is involved in inflammatory and immune responses, it also has cytopathologic potential if not tightly controlled. In Bordetella pertussis infection, NO mediates the respiratory epithelial pathology that is a hallmark of the pertussis syndrome. Tracheal cytotoxin (TCT) released by B. pertussis triggers the production of an inducible NO synthase (iNOS) within tracheal epithelial cells, which produce the NO ultimately responsible for their destruction. The induction of iNOS is most likely due to the cytokine interleukin-1, which is generated intracellularly in response to TCT; this cytokine, like TCT, can reproduce the pathology caused by B. pertussis infection. Similar epithelial destruction is observed in asthma, but the precise mechanism of damage remains incompletely defined. It is possible that NO induced by proinflammatory cytokines in the asthmatic respiratory epithelium plays a central role in the observed epithelial damage in asthma as it does in pertussis.
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PMID:Autotoxicity of nitric oxide in airway disease. 887 43

Endothelial dysfunction caused by the early atherosclerotic process or by endothelial exposure to atherogenic lipids, including lysophosphatidylcholine (lysoPC), is characterized by a selective impairment of responses mediated by the pertussis toxin-sensitive Gi-2 protein. Experiments were performed to analyze the mechanisms underlying this effect. Bradykinin (BK: Gi-2 protein-independent), serotonin (5-HT: Gi-2 protein-dependent), or direct activation of the G(i-2)-protein by mastoparan increased the release of endothelium-derived nitric oxide (EDNO) from porcine arterial endothelial cells (EC). LysoPC decreased the release of EDNO caused by 5-HT, but did not affect the response to BK or mastoparan. LysoPC did not increase production of superoxide radicals detected by lucigenin-enhanced chemiluminescence. Western blot analysis showed no difference in the level of immunoreactive Gi alpha-2 between control and lysoPC-treated cells. Activation of the Gi-2 protein by serotonergic or alpha 2-adrenoceptor stimulation decreased the pertussis toxin-catalyzed ADP-ribosylation of Gi alpha-2 protein in membranes from control but not lysoPC-treated cells. However, direct activation of the Gi-2 protein by mastoparan inhibited the ADP-ribosylation in membranes from control and lysoPC-treated cells. The toxin-catalyzed reaction was reduced in lysoPC-treated cells or lysoPC-treated membranes. LysoPC reduced the ability of endothelin to increase GTP gamma S binding to the Gi-2 protein but did not affect the activity of mastoparan. These results suggest that lysoPC inhibits a pertussis toxin-sensitive signaling pathway in EC by an effect consistent with receptor:Gi-2-protein uncoupling.
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PMID:Analysis of lysophophatidylcholine-induced endothelial dysfunction. 887 79


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