UMLS:C0043167 - FACTA Search

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Query: UMLS:C0043167 (pertussis)
19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ATP stimulates arachidonic acid mobilization and eicosanoid production in cultured astrocytes via P2Y-purinergic receptors. To assist in determining the mechanism of phospholipase A2 activation and the role of calcium in eicosanoid production, cultures were pretreated with pertussis toxin (PTx). ATP-evoked eicosanoid release was inhibited by PTx in a concentration-dependent fashion. Inositol phospholipid hydrolysis was partially attenuated by PTx, but the concentrations required were approximately 50 times greater than those for inhibition of eicosanoid production, suggesting that phospholipase C activation is not necessary for eicosanoid synthesis. Stimulation of eicosanoid release by other P2Y-purinergic receptor agonists was also inhibited by PTx; however, PTx had no effect on eicosanoid release evoked by ionomycin or thapsigargin, nor did it affect ATP-stimulated calcium influx or mobilization from intracellular stores. Increases in intracellular free calcium concentration alone were insufficient to stimulate eicosanoid production, but maximal production was dependent upon the concentration of extracellular calcium. These results suggest that the P2Y-purinergic receptor is coupled to phospholipase A2 via a guanine nucleotide-binding protein, and that extracellular calcium may also be involved in the synthesis of eicosanoids by astrocytes.
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PMID:Purinergic P2Y receptors on astrocytes are directly coupled to phospholipase A2. 838 60

Release of mucins from cultured airway surface epithelial cells can be stimulated by extracellular ATP via a P2-purinergic receptor-mediated mechanism (K. C. Kim and B. C. Lee. 1991. Br. J. Pharmacol. 103:1053-1056). In this report, we studied the mechanism by which extracellular ATP induces the mucin release. We found that: (1) ATP increased both mucin release and generation of inositol phosphates in a dose-dependent fashion, and their dose-effect relationships were almost superimposed; (2) the increases in both mucin release and the phosphatidylinositol phosphate (PI) turnover by extracellular ATP were partially, but almost equally, blocked by the pretreatment with pertussis toxin (42% for mucin release and 44% for PI turnover). We conclude that in cultured airway goblet cells extracellular ATP stimulates mucin release by a signal transduction mechanism, which seems to involve coupling of ATP-activated P2 purinoceptors with phospholipase C, at least in part, via pertussis toxin-sensitive GTP-binding proteins. This may be an important finding in understanding the regulation of mucin release by airway goblet cells, since a number of agents present in the airway could influence this signal transduction pathway and subsequently modulate the mucin secretion.
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PMID:Involvement of a signal transduction mechanism in ATP-induced mucin release from cultured airway goblet cells. 842 4

Schwann cells play an important role in both the development and regeneration of peripheral nerves. Proliferation and differentiation of Schwann cells are critically dependent on changes in the levels of cAMP. ATP is a fast excitatory transmitter in the peripheral nervous system, inducing depolarization of the vagus nerve through occupancy of P2-purinergic receptors. In the present study we demonstrate that extracellular ATP stimulates phospholipase C and inhibits adenylate cyclase activities in cultured Schwann cells. Addition of ATP inhibited, in a concentration-dependent manner, forskolin- or isoprenaline-stimulated adenylate cyclase activity. The rank order of potency corresponding to different purinergic receptor agonists was 2-methylthio-ATP > ATP = ADP > or = adenosine 5'-[gamma-thio]triphosphate (ATP[S]) > UTP, consistent with the involvement of a P2y subtype. Adenosine and adenosine 5'-[alpha,beta-methylene]-triphosphate (pp[CH2pA) were ineffective. Preincubation with pertussis toxin completely blocked this inhibitory effect. When Schwann cells were pre-labelled with myo-[3H]inositol and incubated in Hanks' balanced salt solution containing Ca2+ and Mg2+, addition of ATP[S] resulted in a concentration-dependent increase in the release of InsP with a concomitant increase in intracellular free [Ca2+] ([Ca2+]i). Under these conditions, the effects of both ATP and UTP were of lower magnitude. Removal of Ca2+ and Mg2+ from the assay medium resulted in a significant increase in the effects of ATP[S], ATP and UTP. The decreased response observed in the presence of both bivalent cations (1.2 mM Ca2+ and 1 mM Mg2+) could not be explained either by increased degradation of ATP by Ca2+/Mg2+-dependent nucleotidases or by cation influx. The rank order of potency for the effects of agonists on phospholipase C activity was ATP[S] = adenosine 5'[gamma-imido]triphosphate > ATP -UTP > ADP, indicating the involvement of a P(2U) receptor subtype in this response. Adenosine, AMP and pp[CH2]pA were ineffective. These results demonstrate that immortalized Schwann cells express P(2U) and P(2Y) purinoceptors, which are coupled to stimulation of phospholipase C and inhibition of adenylate cyclase, respectively. Our observations unveil signal-transduction pathways that may be used by ATP to regulate proliferation and differentiation of Schwann cells, and ultimately to influence nerve homeostasis.
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PMID:P2-purigenic receptors regulate phospholipase C and adenylate cyclase activities in immortalized Schwann cells. 867 70

In this study, we have demonstrated that P2-purinoreceptor agonists evoke oscillatory intracellular calcium ([Ca2+]i) responses in human granulosa-lutein cells (GLCs). Intracellular calcium was measured using microspectrofluorimetric techniques. ATP at concentrations of 1-100 microM increased [Ca2+]i, whereas neither adenosine nor AMP evoked changes in [Ca2+]i. The nonhydrolysable ATP analogue, ATP gamma S, also elevated [Ca2+]i with an efficacy similar to that of ATP, indicating that the changes in Ca2+ were not due to ATP hydrolysis, but that human GLCs possess functional P2-purinoreceptors. Uridine triphosphate (UTP) was equipotent to ATP at stimulating [Ca2+]i, and both ATP and UTP were consistently more effective at eliciting a response than ADP, suggesting that human GLCs possess the P2U class of purinergic receptors (ATP = UTP > > ADP > > AMP = adenosine). We have demonstrated that the purinergic agonist-induced changes in [Ca2+]i involve both Ca2+ influx and Ca2+ mobilization from cytosolic stores. Prolonged ATP treatment in Ca(2+)-free buffer (1 mM EGTA) still evokes transient oscillatory changes in [Ca2+]i in a pertussis toxin-insensitive manner. In Ca(2+)-containing conditions, the sustained phase of the response was generally unaffected by verapamil (10 microM), suggesting that influx is not occurring through voltage-dependent Ca(2+)-channels. These findings are consistent with the hypothesis that ATP and other P2-purinergic receptor agonists elicit changes in [Ca2+]i in human ovarian cells and that these events are initiated by the release of Ca2+ from cytosolic stores, and sustained by extracellular calcium ([Ca2+]e) influx. This is the first time that oscillatory patterns of [Ca2+]i have been reported in human GLCs.
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PMID:P2-purinoreceptor evoked changes in intracellular calcium oscillations in single isolated human granulosa-lutein cells. 875 43

Extracellular ATP has been reported to exert mitogenic and contractile effects on cultured renal mesangial cells (MCs). Since it is possible that these actions involve changes in the cAMP second messenger system, we examined the effect of extracellular nucleotides on the accumulation of cAMP in rat MCs. ATP, UTP and adenosine 5'-0-(3-thio)triphosphate (ATP gamma S) (100 microM) had no significant effects on baseline cAMP levels, but inhibited forskolin-stimulated accumulation of cAMP by 21-75% in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Maximal inhibitory effects were observed at 100 microM of ATP gamma S with a threshold dose of 1 microM. ATP gamma S, ATP and UTP were the most potent inhibitors indicating stimulation of the P2u receptor. The P2x agonists adenosine 5'-(alpha, beta-methylene) triphosphate and adenosine 5'-(beta, gamma-methylene) triphosphate, and the P2y agonist 2-methylthio-ATP did not affect cAMP accumulation. Treatment with the P2 receptor antagonist suramin (200 microM) reduced the inhibition by 58%. The inhibitory effects of the nucleotides were significantly attenuated by preincubation with pertussis toxin (10-100 ng/ml). Inhibition of phospholipase C and protein kinase C did not prevent the inhibitory effect of the nucleotides. Inhibitors of forskolin-stimulated cAMP accumulation had different effects on DNA synthesis in cultured MCs as measured by 3H-thymidine uptake at 48 h: ATP, ATP gamma S and the inhibitor of adenylyl cyclase, SQ 22536, stimulated DNA synthesis in MCs, while UTP showed no significant mitogenic effect. Agents which increased baseline levels of intracellular cAMP (forskolin, IBMX, dibutyryl-cAMP) significantly diminished DNA synthesis in MCs. The results indicate that the P2u-purinergic receptor mediates inhibition of forskolin-induced cAMP accumulation which is likely due to inhibition of adenylyl cyclase. This effect appears to be partially mediated by PTX-sensitive G proteins. While the increase in cAMP accumulation is anti-mitogenic, inhibition of cAMP accumulation by P2u receptors is not correlated with MC growth control. Thus, additional mechanisms other than inhibition of cAMP accumulation by P2u receptors are likely to be involved in the mitogenesis of extracellular ATP.
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PMID:P2U-purinergic receptor activation mediates inhibition of cAMP accumulation in cultured renal mesangial cells. 886 79

Signal transduction via P2 purinergic receptors was investigated in HSG cells, a continuous cell line originally derived from an irradiated human salivary gland. Ligand specificity for nucleotide receptors in HSG cells was investigated with various nucleotides and their analogues. Inositol 1,4,5-trisphosphate (IP3) production was significantly increased by ATP, UTP and ATP gamma S. The ligand specificity of this effect agreed well with that of the P2U purinergic receptor. On the other hand, 45Ca2+ influx was stimulated by ATP, UTP > ATP gamma S, ADP, UDP > ADP beta S > AMPPNP, GTP, TTP > CTP, GDP, TDP, AMPPCP, AMPCPP. This ligand specificity of 45Ca2+ influx was much broader than IP3 production. Also pertussis and cholera toxin had no effect on both IP3 production and 45Ca2+ influx by ATP or UTP. 3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (Bz-ATP) stimulates 45Ca2+ influx more effectively than IP3 formation. A 53-kDa membrane protein was photolabelled with [alpha-32P]Bz-ATP. This 53-kDa protein is a putative P2 purinergic receptor. In particular, the labelling was inhibited by a ligand profile that corresponded to that for 45Ca2+ influx. These findings suggest that nucleotides stimulate 45Ca2+ influx and IP3 formation by separate pathways via pertussis and cholera toxin-insensitive G proteins. Thus, in HSG cells, IP3 formation is coupled to the P2U subclass, while 45Ca2+ influx is coupled to another subclass, such as P2X, that regulates calcium channels.
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PMID:A calcium channel in human submandibular duct cell line, HSG cells, not regulated by P2U purinergic receptor-mediated intracellular calcium mobilization. 934 17

The arachidonic acid metabolites produced by thymic epithelial cells play a pivotal role in thymocyte development. We have discovered that ATP and TGF-alpha regulate the arachidonic acid metabolism in TEA3A1 rat thymic epithelial cells by activating phospholipase A2 enzymatic activity. Our present study demonstrates that ATP and its nonhydrolyzable analog ATPgammaS stimulate both prostaglandin E2 production and Ca2+ influx in TEA3A1 cells. The stimulation of prostaglandin E2 production and Ca2+ influx by ATP is inhibited by pertussis toxin treatment, indicating that ATP mediates its effect by binding to a G-protein-coupled purinergic receptor. Treatment of cells with ATPgammaS and transforming growth factor-alpha results in a synergistic activation of phospholipase A2 and stimulation of prostaglandin E2 production. Results from experiments using an inhibitor of receptor-mediated Ca2+ influx indicate that the synergistic stimulation of prostaglandin E2 production by ATPgammaS and transforming growth factor-alpha requires ATPgammaS-mediated Ca2+ influx. The inhibitor of tyrosine kinase genistein also blocked both ATPgammaS- and ATPgammaS plus transforming growth factor-alpha-mediated stimulation of prostaglandin E2 production, indicating that the activation of phospholipase A2 may involve a protein tyrosine phosphorylation step.
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PMID:Regulation of arachidonic acid release and prostaglandin E2 production in thymic epithelial cells by ATPgammaS and transforming growth factor-alpha. 975 37

1. Our aim was to assess whether ATP-induced inward currents in microglia are due to a single or more than one purinergic receptor. The ATP dose-response curve showed two components, whose presence might be due to the activation of high and low affinity receptors. 2. The P2Z/P2X7 specific receptor agonist benzoylbenzoyl-ATP (Bz-ATP) and some P2 receptor agonists were tested. The rank order of potency was Bz-ATP >> ATP = 2-methylthio-ATP (2-MeSATP) > alpha, beta-methylene ATP (alpha,beta-meATP) >= ADP. beta, gamma-MethyleneATP (beta,gamma-meATP), UTP and adenosine were ineffective. 3. The non-specific P2 receptor antagonist suramin antagonized by 92 +/- 2 % the inward current induced by 100 microM ATP, and by 51 +/- 8 and 68 +/- 6 % those induced by 3 mM ATP and 100 microM Bz-ATP, respectively. The P2Z/P2X7 antagonist oxidized ATP (oATP) almost abolished the inward current induced by 3 mM ATP or Bz-ATP, but was ineffective against 100 microM ATP. 4. Inward currents induced by low ATP concentrations (<= 100 microM) were generally followed by an almost complete and irreversible desensitization, while those elicited by ATP >= 1 mM showed only a partial decline. Interestingly, the inward current induced by 100 microM 2-MeSATP showed a large desensitization, while that induced by Bz-ATP did not. 5. In voltage-ramp experiments, the 100 microM ATP-induced current exhibited a slight inward rectification more visible at negative potentials, while the 3 mM ATP-induced current did not. 6. ATP induced a fast and large increase in [Ca2+] that promptly recovered in the continuous presence of low ATP doses, but did not recover in high ATP doses. As with desensitization, the response to Bz-ATP mimicked that of high doses of ATP. 7. When Ca2+ mobilization due to P2Y receptors was blocked by thapsigargin-induced Ca2+ depletion or by pertussis toxin treatment, 10 microM ATP was still able to induce a Ca2+ transient, which represented the contribution of the Ca2+ influx induced by P2X receptors 8. In conclusion, the inward currents and a fraction of the Ca2+ transients induced by ATP in microglia are due to at least two ATP-sensitive receptor channel types, whose different properties and sensitivity to ATP may be associated with different functional roles.
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PMID:Two different ionotropic receptors are activated by ATP in rat microglia. 1045 86

Phospholipase D (PLD) is present in human placental tissue. Since purinergic receptor agonists activate PLD in many different cell types, we evaluated the purinergic activation of the enzyme in cultured trophoblasts from the placenta. We found that P(2) receptor agonists stimulate PLD. The preferred ligand for P(2X7) (P(2Z)) receptor subtype, BzBz-ATP (10(-3)M ), induced the enzyme more than ten times over basal (unstimulated) activity, while ATP caused a much smaller increase. ATPgammaS, ADP and UTP were even less effective, compared to BzBz-ATP or ATP. AMP and alpha,beta-methyl-ATP, a P(2X) agonist that is uniquely inactive on the P(2X7) subtype, had no effect. This represents the first suggestion of the presence of the P(2X7) type of receptor in human trophoblasts that was directly confirmed by immunoblot detection. The action of BzBz-ATP was dependent upon the presence of calcium in the culture medium and was inhibited by high (5m M ) Mg(++) concentration. P(2X7) receptor subtype specific antagonists, ATP-2',3'-dialdehyde (o-ATP), CBB and the broad specificity P(2) inhibitor PPADS inhibited the effect of BzBz-ATP. Pertussis toxin treatment did not inhibit the effect. Down-regulation of cPKC/nPKC isoforms by prolonged PMA treatment (36 h, 10(-7)M ) prevented the stimulation of PLD by P(2) agonists or the calcium ionophore A-23187. PLA(2) inhibitors did not block the effect of BzBz-ATP. The possibility for a calcium influx related interdependence of PLC and PLD was evaluated. For PLC activation, UTP and ATP surpassed BzBz-ATP, while ionophore did not elevate PLC (assessed by IP(3) measurements). This suggested the predominance of a P(2Y2) receptor in the whole cell in gross activation of PLC. PLD was affected with a reversed order of potency. These results and the dependence of PLD on PKC activity implies that a restricted, membrane localized calcium flux activates PKC and in turn, mediates the P(2X7) dependent stimulation of PLD. This may have implications for physiologic regulation of trophoblast function.
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PMID:Regulation of phospholipase D in human placental trophoblasts by the P(2) purinergic receptor. 1236 78

The intracellular signalling pathways and molecular mechanisms responsible for P2-purinoceptor-mediated chloride (Cl(-)) currents (I(Cl,ATP)) were studied in mouse ventricular myocytes. In standard NaCl-containing extracellular solutions, extracellular ATP (100 microm) activated two different currents, I(Cl,ATP) with a linear I-V relationship in symmetrical Cl(-) solutions, and an inwardly rectifying cation conductance (cationic I(ATP)). Cationic I(ATP) was selectively inhibited by Gd(3+) and Zn(2+), or by replacement of extracellular NaCl by NMDG; I(Cl,ATP) was Cl(-) selective, and inhibited by replacement of extracellular Cl(-) by Asp(-); both currents were prevented by suramin or DIDS pretreatment. In GTPgammaS-loaded cells, I(Cl,ATP) was irreversibly activated by ATP, but cationic I(ATP) was still regulated reversibly. GDPbetaS prevented activation of the I(Cl,ATP,) even though pertussis toxin pretreatment did not modulate I(Cl,ATP). These results suggest that activation of I(Cl,ATP) occurs via a G-protein coupled P2Y purinergic receptor. The I(Cl,ATP) persistently activated by GTPgammaS, was inhibited by glibenclamide but not by DIDS, thus exhibiting known pharmacological properties of cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channels. In ventricular cells of cftr(-/-) mice, extracellular ATP activated cationic I(ATP), but failed to activate any detectable I(Cl,ATP). These results provide compelling evidence that activation of CFTR Cl(-) channels in mouse heart are coupled to G-protein coupled P2Y purinergic receptors.
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PMID:P2Y purinergic receptor regulation of CFTR chloride channels in mouse cardiac myocytes. 1497 3

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