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)

1. Experiments were made to investigate mechanisms by which adenosine 5'-trisphosphate (ATP) enhanced vasomotion in mesenteric lymphatic vessels isolated from young guinea-pigs. 2. ATP (10-8 - 10-3 M) caused a concentration-dependent increase of perfusion-induced vasomotion with the endothelium mediating a fundamental role at low ATP concentrations (10-8 - 10-6 M). 3. The response to 10-6 M ATP showed tachyphylaxis when applied at intervals of 10 min but not at intervals of 20 or 30 min. 4. Suramin (10-4 M) or reactive blue 2 (3x10-5 M) but not PPADS (3x10-5 M) abolished the excitatory response to 10-6 M ATP confirming an involvement of P2 purinoceptors. 5. The excitatory response to 10-6 M ATP was abolished by treatment with either pertussis toxin (100 ng ml-1), antiflammin-1 (10-9 M), indomethacin (3x10-6 M) or SQ29548 (3x10-7 M), inhibitors of specific G proteins, phospholipase A2, cyclo-oxygenase and thromboxane A2 receptors respectively. 6. ATP simultaneously induced a suramin-sensitive inhibitory response, which was normally masked by the excitatory response. ATP-induced inhibition was mediated by endothelium-derived nitric oxide (EDNO) as the response was abolished by NG-nitro-L-arginine (L-NOARG; 10-4 M), an inhibitor of nitric oxide synthase. 7. We conclude that ATP modulates lymphatic vasomotion by endothelium-dependent and endothelium-independent mechanisms. One of these is a dominant excitation caused through endothelial P2 purinoceptors which because of an involvement of a pertussis toxin sensitive G-protein may be of the P2Y receptor subtype. Their stimulation increases synthesis of phospholipase A2 and production of thromboxane A2, an arachidonic acid metabolite which acts as an endothelium-derived excitatory factor.
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PMID:Evidence that the ATP-induced increase in vasomotion of guinea-pig mesenteric lymphatics involves an endothelium-dependent release of thromboxane A2. 1045 15

Adenosine has cardioprotective effects against ischemia, and newborn hearts show high resistance to ischemia. The effects of purinoceptor stimulation by adenosine and ATP on the L-type Ca2+ current (ICa) were examined in atrial cells from neonate and adult rabbits. ICa was measured by the membrane-perforated patch method. Adenosine inhibited the isoproterenol-stimulated ICa more potently in neonate cells than in adult cells. The high sensitivity of neonate myocytes to adenosine was accompanied not only by an increased maximum response but also by a lower IC50 concentration. ATP also inhibited isoproterenol-stimulated ICa. The effect of ATP on neonate cells was stronger than that on adult cells at high concentrations (greater than or = 100 microM). The effect of adenosine was antagonized by an A1 adenosine receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). DPCPX or an ecto-5'-nucleosidase inhibitor (alpha,beta-methylene-ADP) blocked most (approximately 60%) of the effect of ATP (30 microM), and co-addition of DPCPX and suramin (P2 receptor blocker) abolished the effect of ATP. Suramin alone did not reduce the effect of ATP significantly in neonate cells. Both the effects of adenosine and ATP were eliminated by pre-treatment with pertussis toxin or by superfusion with forskolin plus 3-isobutyl-1-methylxanthine (IBMX). Inhibitors of the nitric oxide-cyclic GMP pathway did not affect the adenosine inhibition of ICa. In summary, neonatal myocardial cells are highly sensitive to adenosine A1 receptor stimulation. ATP stimulates both the adenosine A1 and P2 receptors. Adenosine A1 receptor stimulation, as a result of hydrolysis of ATP, predominantly mediates the effect of ATP, and the role of P2 receptors in the ATP inhibition of ICa is relatively small in neonate cells. The high sensitivity to adenosine may contribute to the ischemic tolerance of newborn hearts.
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PMID:Increased sensitivity of neonate atrial myocytes to adenosine A1 receptor stimulation in regulation of the L-type Ca2+ current. 1110 15

1. In glioma C6 cells, the stimulation of P2Y receptors by ADP, ATP and UTP initiated an increase in the intracellular Ca2+ concentration, in a process that involved the release of Ca2+ from InsP(3)-sensitive store and the capacitative, extracellular Ca2+ entry. The presence of external Ca2+ was not necessary to elevate Ca(2+). 2. The rank order of potencies of nucleotide analogues in stimulating [Ca2+](i) was: 2MeSADP > ADP > 2MeSATP = 2ClATP > ATP > UTP. alpha,beta-Methylene ATP, adenosine and AMP were ineffective. 3. ADP and UTP effects were additive, while actions of ATP and UTP were not additive on [Ca2+](i) increase. Similarly, cross-desensitization between ATP and UTP but not between ADP and UTP occurred. 4. Suramin, a non-specific nucleotide receptors inhibitor, antagonized ATP-, UTP- and ADP-evoked Ca2+ responses. PPADS, a selective antagonist of the P2Y(1) receptor-generated InsP(3) accumulation, decreased ADP-initiated Ca2+ response with no effect on ATP and UTP. 5. Pertussis toxin (PTX) reduced ADP- and ATP-induced Ca2+ increases. Short-term treatment with TPA, inhibited both ATP and ADP stimulatory effects on [Ca2+](i). 6. ADP inhibited isoproterenol-induced cyclic AMP accumulation. PTX blocked this effect, but PPADS did not. 7. RT - PCR analysis revealed the molecular identity of P2Y receptors expressed by glioma C6 cells to be both P2Y(1) and P2Y(2). 8. It is concluded that both P2Y(1) and P2Y(2) receptors co-exist in glioma C6 cells. ADP acts as agonist of the first, and ATP and UTP of the second one. Both receptors are linked to phospholipase C (PLC).
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PMID:Two subtypes of G protein-coupled nucleotide receptors, P2Y(1) and P2Y(2) are involved in calcium signalling in glioma C6 cells. 1115 87

Aluminum hydroxide and incomplete Freund's adjuvant (IFA) are the only adjuvants approved for human use. Both are T helper 2 (Th2) adjuvants, however, T helper 1 (Th1) immunity is induced if microbial products such as mycobacteria, CpG's, or bacterial toxins are included in the adjuvant preparation. The usefulness of bacterial toxins, such as Pertussis toxin (PT) or Cholera toxin (CT), as adjuvants for human vaccination is limited by toxic side effects and high immunogenicity. Hence, we asked whether or not the adjuvant activity of bacterial toxins on Th1 and Th2 immunity could be mimicked by chemical compounds of small molecular weight and less immunogenicity. In the present study, we show that Suramin, a small molecular weight naphthylurea, which mainly acts on G-proteins and on P2X/P2Y receptors, promotes expansion of hen eggwhite lysozyme (HEL)-specific Th1 and Th2 cells upon immunization of BALB/c mice with HEL in aluminum hydroxide (alum). The results indicated that the adjuvant effects of Suramin on T cell responses were mediated by enhancing the expression of MHC class II and costimulatory molecules on antigen presenting cells (APCs), and by increasing their pro-inflammatory cytokine production. Together, the results suggest that small molecular weight compounds such as Suramin could be used as alternative vaccine adjuvants.
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PMID:Suramin has adjuvant properties and promotes expansion of antigen-specific Th1 and Th2 cells in vivo. 1497 56

Most current cell-based models for examining the regulation of mucin secretion demonstrate low signal-to-noise ratios, making experimental manipulation and data interpretation difficult. Using adenosine triphosphate (ATP) as a mucin secretagogue, we have developed a model of agonist-induced mucin secretion in differentiated human bronchial epithelial cells. Mucin secretory signals were estimated using enzyme-linked lectin assay, and typical signals of 300-400% of baseline were observed in response to a 30-min exposure to ATP (100 microM). ATP and uridine triphosphate equipotently stimulated mucin secretion consistent with mediation via P2Y2 receptor activation. Suramin and AR-C118925XX, a competitive P2Y2 receptor antagonist, inhibited adenosine 5'-o-(3-thiotriphosphate) (ATP-gammaS)-induced mucin secretion. A selective Gq G-protein antagonist (GP-ANT)-2A completely abrogated ATP-gammaS-induced mucin secretion. Pertussis toxin and the G(i/o)-specific, GP-ANT-2, had no effect. The phospholipase C inhibitor, D609, and the protein kinase C inhibitor, calphostin C, substantially inhibited ATP-gammaS-induced mucin secretion. Phorbol myristate acetate also stimulated mucin secretion in a calphostin C-sensitive manner. ATP-gammaS-induced mucin secretion was inhibited by the Ca2+ chelator, 1,2-bis(o-aminophenoxy) ethane-N,N,N',N'-tetra-acetic acid tetra (acetoxymethyl) ester. Ionomycin and thapsigargin both stimulated mucin secretion. Our data are broadly consistent with known G-protein-coupling and downstream signaling events associated with the P2Y2 receptor. The exceptional signal-to-noise ratios obtained using this model have permitted clear evaluation of the involvement of these mechanisms in agonist-induced mucin secretion from differentiated human bronchial epithelial cells.
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PMID:Nucleotide-mediated mucin secretion from differentiated human bronchial epithelial cells. 1523 88

During normal cell metabolism the production of intracellular ATP is associated with the generation of reactive oxygen species (ROS), which appear to be important signalling molecules. Both ATP and ROS can be released extracellularly by skeletal muscle during intense activity. Using voltage clamp recording combined with imaging and biochemical assay of ROS, we tested the hypothesis that at the neuromuscular junction extracellular ATP generates ROS to inhibit transmitter release from motor nerve endings. We found that ATP produced the presynaptic inhibitory action on multiquantal end-plate currents. The inhibitory action of ATP (but not that of adenosine) was significantly reduced by several antioxidants or extracellular catalase, which breaks down H2O2. Consistent with these data, the depressant effect of ATP was dramatically potentiated by the pro-oxidant Fe2+. Exogenous H2O2 reproduced the depressant effects of ATP and showed similar sensitivity to anti- and pro-oxidants. While NO also inhibited synaptic transmission, inhibitors of the NO-producing cascade did not prevent the depressant action of ATP. The ferrous oxidation in xylenol orange assay showed the increase of ROS production by ATP and 2-MeSADP but not by adenosine. Suramin, a non-selective antagonist of P2 receptors, and pertussis toxin prevented the action of ATP on ROS production. Likewise, imaging with the ROS-sensitive dye carboxy-2',7'-dichlorodihydrofluorescein revealed increased production of ROS in the muscle treated with ATP or ADP while UTP or adenosine had no effect. Thus, generation of ROS contributed to the ATP-mediated negative feedback mechanism controlling quantal secretion of ACh from the motor nerve endings.
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PMID:Reactive oxygen species contribute to the presynaptic action of extracellular ATP at the frog neuromuscular junction. 1577 19

Sphingosine-1-phosphate (S1P) is a pluripotent lipid mediator that transmits signals through a family of G protein-coupled receptors to control diverse biological processes. Here, we investigated the effects of S1P on the levels of intracellular calcium and cAMP in differentiated rat white adipocytes and two important aspects of adipocyte-specific physiology, lipolysis and leptin production. In adipocytes, S1P signaling pathway was functionally linked to phospholipase C via pertussis-toxin-sensitive G protein. Interestingly, at higher S1P concentration (1-30 microM), it also induced cAMP generation in a concentration-dependent manner, which was pertussis toxin insensitive and was mimicked by dihydro-S1P and sphingosylphosphoryl-choline but not by its related metabolites, ceramide and sphingosine, or by its structural analogs, phyto-S1P and lysophosphatidic acid. Suramin, a known inhibitor of ligand-receptor interactions, reduced S1P-induced cAMP generation by 60% of control, whereas forskolin-induced cAMP increase was not affected by treatment with suramin. The S1P-induced cAMP generation was functionally linked to cAMP response element-binding protein phosphorylation. Finally, S1P significantly reduced insulin-induced mRNA of ob gene and leptin secretion, whereas S1P increased glycerol release from adipocytes. Both effects of S1P were reversed by a selective adenylyl cyclase inhibitor, SQ22536, without significantly affecting basal values. In conclusion, extracellular S1P elicits the elevation of cytosolic Ca2+ and cAMP with a distinct concentration dependency, and S1P-induced cAMP generation may be mediated by S1P-selective receptors rather than intracellular targets, and the activated adenylyl cyclase-cAMP signaling pathways subsequently increase lipolysis and decrease insulin-induced leptin production in rat white adipocytes.
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PMID:Sphingosine-1-phosphate modulates both lipolysis and leptin production in differentiated rat white adipocytes. 1697 28

The effects of sphingosine 1-phosphate (S1P) on prostaglandin I(2) (PGI(2)) production and cyclooxygenase (COX) expression in cultured rat vascular smooth muscle cells (VSMCs) were investigated. S1P stimulated PGI(2) production in a concentration-dependent manner, which was completely suppressed by NS-398, a selective COX-2 inhibitor, as determined by radioimmunoassay. S1P stimulated COX-2 protein and mRNA expressions in a concentration- and time-dependent manner, while it had no effect on COX-1 expression. S1P(2) and S1P(3) receptors mRNA were abundantly expressed in rat VSMCs. Suramin, an antagonist of S1P(3) receptor, almost completely inhibited S1P-induced COX-2 expression. Pretreatment of VSMCs with pertussis toxin (PTX) partially, but significantly inhibited S1P-induced PGI(2) production and COX-2 expression. S1P also activated extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). However, neither PD 98059, a selective inhibitor of ERK activation, nor SB 203580, a selective inhibitor of p38 MAPK, had a significant inhibitory effect on S1P-induced COX-2 expression, suggesting that the MAPK activation does not play main roles in S1P-induced COX-2 induction. S1P-induced COX-2 expression was inhibited by PP2, an inhibitor of Src-family tyrosine kinase, Ca(2+) depletion, and GF 109203X, an inhibitor of protein kinase C (PKC). These results suggest that S1P stimulates COX-2 induction in rat VSMCs through mechanisms involving Ca(2+)-dependent PKC and Src-family tyrosine kinase activation via S1P(3) receptor coupled to PTX-sensitive and -insensitive G proteins.
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PMID:Sphingosine 1-phosphate induces cyclooxygenase-2 via Ca2+-dependent, but MAPK-independent mechanism in rat vascular smooth muscle cells. 1738 52


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