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)

Adenosine and pertussis vaccine each significantly suppressed the in vitro lymphocyte response to phytohemagglutinin (PHA) in both asthmatic and non-asthmatic subjects. On the other hand, pertussis vaccine significantly enhanced the response of the lymphocytes treated with a lower concentration of adenosine both in asthmatic and non-asthmatic subjects. It was also shown that lymphocytes from asthmatic and non-asthmatic subjects responded similarly to the modulating effect of adenosine and/or pertussis vaccine on PHA stimulation. These data give further evidence for the complex interplay of the vaccine with endogenous adenosine.
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PMID:Effect of adenosine and pertussis vaccine on lymphocyte response in vitro to phytohemagglutinin in asthmatic and non-asthmatic subjects. 340 Sep

Adenosine Ri receptors and inhibitory guanine-nucleotide-regulatory components were solubilized from rat cerebral-cortical membranes with sodium cholate. (-)-N6-Phenylisopropyl[2,8-3H]adenosine [( 3H]PIA) binds with high affinity to the soluble receptors, which retain the pharmacological specificity of adenosine Ri receptors observed in membranes. The binding is regulated by bivalent cations and guanine nucleotides. Bivalent cations increase [3H]PIA binding by increasing both the affinity and the apparent number of receptors. Guanine nucleotides decrease agonist binding by increasing the dissociation of the ligand-receptor complex. Adenosine agonists stabilize the high-affinity form of the soluble receptor. The hydrodynamic properties of the adenosine receptor were determined with cholate extracts of membranes that were treated with [3H]PIA. Sucrose-gradient-centrifugation analysis indicates that the receptor has a sedimentation coefficient of 7.7 S. The receptor is eluted from Sepharose 6B columns with an apparent Stokes radius of 7.2 nm. Labelling of either sucrose-gradient or gel-filtration-column fractions with pertussis toxin and [32P]-NAD+ reveals that both the 41,000- and 39,000-Mr substrates overlap with the receptor activity. These studies suggest that the high-affinity adenosine-receptor-binding activity in the cholate extract represents a stable R1-N complex.
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PMID:Hydrodynamic properties of adenosine Ri receptors solubilized from rat cerebral-cortical membranes. 343 74

Adenosine, via interaction with A1 adenosine receptors, increases insulin sensitivity and inhibits lipolysis in adipocytes. To investigate regulation of this system, adipocytes were incubated for up to 72 h with the nonmetabolizable adenosine receptor agonist, N6-phenylisopropyl adenosine (PIA). Adenosine receptors were measured by the binding of 125I-hydroxyphenylisopropyl adenosine to membranes. PIA down-regulated adenosine receptors, decreasing the number of binding sites with no change in affinity. Adipocytes were incubated for 48 h without or with 100 nM PIA to down-regulate the A1 receptors by approximately 60%. The cells were washed, and lipolysis and glucose transport were assessed. The ability of PIA to inhibit lipolysis was markedly attenuated in the down-regulated cells. Furthermore, the EC50 of insulin was increased approximately 3-fold in the PIA-treated cells. 125I-Insulin binding to the PIA-treated cells was unchanged, demonstrating that the decreased insulin sensitivity is not due to decreased insulin receptor binding. Pertussis toxin catalyzed ADP-ribosylation of a 41-kDa protein thought to be the alpha-subunit of Gi. This 41-kDa protein was decreased in membranes from cells treated with PIA, with a maximal 50% loss. This suggests that Gi is down-regulated and that loss of both the A1 adenosine receptor and Gi are involved in the metabolic changes observed after PIA treatment.
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PMID:Adenosine receptor down-regulation and insulin resistance following prolonged incubation of adipocytes with an A1 adenosine receptor agonist. 368 Feb 21

Adenosine, acting via A1 adenosine receptors, can inhibit adenylate cyclase activity in adipocytes. To assess the effects of chronic adenosine agonist exposure on the A1 adenosine receptor system of adipocytes, rats were infused with (-)-phenylisopropyladenosine or vehicle for 6 days and membranes were prepared. Basal as well as isoproterenol-, sodium fluoride-, and forskolin-stimulated adenylate cyclase activities were significantly increased (approximately 2-fold) in membranes from treated animals. (-)-Phenylisopropyladenosine-mediated inhibition of forskolin-stimulated adenylate cyclase activity was significantly (p = 0.0001) attenuated in membranes from treated rats (20.1 +/- 2.1% inhibition) versus controls (31.6 +/- 2.3% inhibition). Prostaglandin E1-induced inhibition of forskolin-stimulated adenylate cyclase activity was also attenuated: 11.7 +/- 3.6 versus 23.2 +/- 4.6% (p = 0.001). Using the A1 adenosine receptor agonist radioligand (-)-N6-(3-[125I]iodo-4-hydroxyphenylisopropyl)adenosine, 32% fewer high affinity binding sites were detected in membranes from treated animals (p less than 0.04). Photoaffinity labeling with N6-2-(3-[125I]iodo-4-azidophenyl)ethyladenosine revealed no gross difference in receptor structure. The number of beta-adrenergic receptors as well as the percentage of receptors in the high affinity state as assessed by (-)-3-[125I]iodocyanopindolol binding were the same in both groups. In membranes from treated rats, the amount of [alpha-32P]NAD incorporated by pertussis toxin into the alpha subunit of the inhibitory guanine nucleotide regulatory protein (Ni) was decreased by 37 +/- 11%. Concurrently, the quantity of label incorporated by cholera toxin into the alpha subunit of the stimulatory guanine nucleotide regulatory protein (Ns) was increased by 44 +/- 14% in treated membranes. Finally, the capacity of Ns solubilized from treated membranes to stimulate adenylate cyclase activity when reconstituted into cyc- S49 lymphoma cell membranes was enhanced by approximately 50% compared to control. Thus, heterologous desensitization, manifested by a diminished capacity to inhibit adenylate cyclase and an enhanced responsiveness to stimulatory effectors, can be induced in the A1 adenosine receptor-adenylate cyclase system of adipocytes. A decrease in Ni alpha subunit concomitant with an increase in Ns alpha subunit quantity and activity may represent the biochemical mechanism of desensitization in this system.
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PMID:Heterologous desensitization of the inhibitory A1 adenosine receptor-adenylate cyclase system in rat adipocytes. Regulation of both Ns and Ni. 380 10

Glial cells are closely associated with synapses and are modulated by neurotransmitters released during synaptic transmission. At many synapses, ATP is released during synaptic transmission and is involved in cell-cell signaling. Since glial cells have purinoceptors, it is possible that ATP mediates synaptic neuron-glia signaling. This work aims at determining which types of purinoceptors are present on perisynaptic Schwann cells, the perisynaptic glial cells at the frog neuromuscular junction, and test their sensitivity to endogenous purines by monitoring the relative changes of intracellular Ca2+. Local application of ATP induced the release of Ca2+ from internal stores. Adenosine induced Ca2+ responses that were blocked by A1 receptor antagonists and mimicked by an A1 receptor agonist and were caused by the release of Ca2+ from internal stores via a pertussis toxin-sensitive G-protein. A2 receptor antagonists had no effect on Ca2+ responses induced by adenosine. Me-S-ATP, an ATP analog, triggered Ca2+ release from internal stores via a pertussis toxin-sensitive G-protein, consistent with the activation of P2Y receptors. L-AMP-PCP, another ATP analog, induced Ca2+ entry mainly through L-type Ca2+ channels by a pertussis toxin-insensitive mechanism, consistent with the activation of P2X receptors. Blockade of adenosine receptors did not affect glial Ca2+ responses induced by nerve evoked transmitter release. However, blockade of ATP receptors reduced the size and increased the delay of the responses. Hence, purinoceptors are present on the perisynaptic Schwann cells and are activated by endogenous ATP released during synaptic transmission.
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PMID:Purinergic receptors and their activation by endogenous purines at perisynaptic glial cells of the frog neuromuscular junction. 747 66

Effects of adenosine on inward current activated by extracellular ATP were examined in rat pheochromocytoma PC12 cells. Adenosine induced two types of modulation on the current activated by 30 microM ATP; a low concentration of adenosine (1 microM) inhibited the current whereas a high concentration (> 10 microM) enhanced the current. Neither the inhibition nor the enhancement was observed in cells pretreated with pertussis toxin (PTX), or in cells dialyzed with guanosine 5'-O-(2-thiotriphosphate) trilithium salt (GDP beta S). In contrast, dialysis with K-252a, a protein kinase inhibitor, abolished the inhibition, but not the enhancement. Adenosine induced similar inhibition and enhancement on ATP-evoked increase in intracellular free Ca2+ concentration. The results suggest that adenosine produces dual modulation on the ATP-activated channels through different mechanisms involving PTX-sensitive GTP-binding proteins.
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PMID:Dual modulation by adenosine of ATP-activated channels through GTP-binding proteins in rat pheochromocytoma PC12 cells. 752 18

Adenosine potentiates mast cell activation, but the receptor type and molecular mechanisms involved have not been defined. We, therefore, investigated the effects of adenosine on the human mast cell line HMC-1. Both the A2a selective agonist CGS21680 and the A2a/A2b nonselective agonist 5'-N-ethylcarboxamidoadenosine (NECA) increased cAMP, but NECA was fourfold more efficacious and had a Hill coefficient of 0.55, suggesting the presence of both A2a and A2b receptors. NECA 10 microM evoked IL-8 release from HMC-1, but CGS21680 10 microM had no effect. In separate studies we found that enprofylline, an antiasthmatic previously thought to lack adenosine antagonistic properties, is as effective as theophylline as an antagonist of A2b receptors at concentrations achieved clinically. Both theophylline and enprofylline 300 micro completely blocked the release of IL-8 by NECA. NECA, but not CGS21680, increases inositol phosphate formation and intracellular calcium mobilization through a cholera and pertussis toxin-insensitive mechanism. In conclusion, both A2a and A2b receptors are present in HMC-1 cells and are coupled to adenylate cyclase. In addition, A2b receptors are coupled to phospholipase C and evoke IL-8 release. This effect is blocked by theophylline and enprofylline, raising the possibility that this mechanism contributes to their antiasthmatic effects.
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PMID:Adenosine A2b receptors evoke interleukin-8 secretion in human mast cells. An enprofylline-sensitive mechanism with implications for asthma. 756 91

1. Adenosine is known to stimulate capillary outgrowth and endothelial cell proliferation, but the underlying mechanism has not been identified. In order to identify the receptor subtype involved, the effects of adenosine receptor agonists and antagonists on human umbilical vein endothelial cell (HUVEC) proliferation were investigated. 2. Raising intracellular adenosine levels by use of the adenosine transport inhibitor, 4-nitrobenzylthioinosine (NBMPR) did not affect cell growth. This observation suggests that stimulation of an extracellular adenosine receptor generates the mitogenic signal. 3. In the presence of adenosine deaminase (ADA), which was used to remove adenosine present in the culture medium, the adenosine receptor agonists N-ethylcarboxamidoadenosine (NECA, non-selective) and CGS21680 (A2A-receptor-selective) stimulated [3H]-thymidine incorporation with a half-maximum effect at about 10 nM, while N6-cyclopentyladenosine (CPA, A1-selective) was about 100 fold less potent. The adenosine receptor antagonist, xanthine amine congener (XAC) produced a concentration-dependent decrease in endothelial cell proliferation with a half-maximum effect at about 10 nM. Hence, stimulation of an endothelial A2A-adenosine receptor seems responsible for the mitogenic signal. 4. In the presence of ADA, isoprenaline is also able to stimulate [3H]-thymidine incorporation with a half maximal effect of about 3 nM, an effect, which is reversed by the highly beta 2-selective antagonist, ICI 118,551. In the absence of ADA, isoprenaline exerts only a minor stimulatory effect. Combination of A2A adenosine and beta 2-adrenoceptor agonists did not further enhance [3H]-thymidine incorporation when compared to the sole addition of each agonist. We therefore conclude that both receptors stimulate endothelial cell proliferation via a common signal transduction pathway. 5. Both receptors are coupled to stimulation of adenylyl cyclase via the stimulatory G protein G8.However, direct activation of downstream effectors in the cyclic AMP-signalling cascade (G8 with cholera toxin, adenylyl cyclase with forskolin, protein kinase A with 8Br-cyclic AMP) not only failed to mimic the action of receptor-activation, but even reduced cell proliferation.6. Similarly, pertussis toxin-treatment which inactivated the Gi 2 protein present in HUVEC and thus inhibited cell proliferation per se, did not impair the ability of A2A-receptor agonists to stimulate cell proliferation. This suggests that the A2A-adenosine and beta2-adrenoceptor-mediated stimulation of endothelial cell proliferation occurs via a mechanism that is independent of G8 and Gi.
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PMID:Stimulation of human umbilical vein endothelial cell proliferation by A2-adenosine and beta 2-adrenoceptors. 759 25

Four native and cloned adenosine receptors (ARs), designated A1AR, A2aAR, A2bAR, and A3AR, have been characterized functionally and by radioligand binding. In the present study, we have used selective antibodies to identify the G protein subunits and phospholipase C (PLC)-beta isoform coupled to A1ARs in smooth muscle membranes and permeabilized muscle cells from rabbit intestine. Immunoblot analysis disclosed the presence of a full complement of G proteins. Adenosine caused contraction of dispersed muscle cells and increases in D-myo-inositol-1,4,5-trisphosphate, intracellular calcium, and cAMP levels. Contraction and the increases in D-myo-inositol-1,4,5-trisphosphate and intracellular calcium levels were abolished by the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine and augmented by the A2 antagonist CGS-15943; the reverse occurred with cAMP. A selective A1AR agonist, cyclopentyladenosine, inhibited forskolin-stimulated cAMP accumulation; the inhibition was reversed by treatment of the cells with pertussis toxin or a G alpha i3-specific antibody. The pattern of inhibition implied coexistence of A1ARs and A2ARs coupled to interactive signaling pathways, with A2ARs mediating activation of adenylyl cyclase and A1ARs mediating activation of PLC and inhibition of adenylyl cyclase. Adenosine-stimulated PLC activity in muscle membranes was selectively blocked by G alpha i3- and G beta-specific antibodies, as well as by a PLC-beta 3-specific antibody, but not by antibodies to other PLC-beta isoforms or G proteins. A combination of maximally effective concentrations of G alpha i3- and G beta-specific antibodies did not elicit greater inhibition than did either alone. In contrast, cholecystokinin-stimulated PLC activity was selectively blocked by PLC-beta 1- and G alpha q/11-specific antibodies. Adenosine-stimulated contraction and 45Ca2+ efflux in permeabilized muscle cells were also selectively blocked by G alpha i3-, G beta-, and PLC-beta 3-specific antibodies, whereas cholecystokinin-stimulated contraction was selectively blocked by PLC-beta 1- and G alpha q/11-specific antibodies. The results indicate that A1ARs are coupled to PLC-beta 3 via both alpha and beta gamma subunits of Gi3.
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PMID:Adenosine A1 receptor-mediated activation of phospholipase C-beta 3 in intestinal muscle: dual requirement for alpha and beta gamma subunits of Gi3. 760 57

Adenosine receptors and the signaling pathways to which they are coupled were examined in dispersed intestinal muscle cells. The receptors were characterized by their ability to induce contraction or relaxation, mobilize Ca2+ and stimulate or inhibit cAMP, in naive cells and in cells where only one receptor type was preserved by selective receptor protection. Adenosine elicited contraction and increased [Ca2+]i and cAMP; the contraction was mimicked by the A1 selective agonist, cyclopentyladenosine. A selective A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine, and pertussis toxin abolished contraction and the increase in [Ca2+]i and augmented the increase in cAMP. Conversely, a preferential A2 antagonist, 9-chloro-2-(2-furyl) [1,2,4]triazolo[1,5-c]quinazolin-5-amine augmented contraction and the increase in [Ca2+]i and abolished the increase in cAMP; a cAMP-kinase inhibitor, Rp-cAMP[S], had a similar effect, augmenting contraction and the increase in [Ca2+]i. Adenosine elicited also relaxation of maximally contracted cells that increased or decreased in parallel with cAMP. The selective A2a agonist, 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido adenosine, was a very weak relaxant agent, and the selective A2a antagonist, 8-(3-chlorostyryl)caffeine, had no effect on adenosine-induced relaxation. In cells where only A1 receptors were preserved, the cAMP response to adenosine was abolished, although contraction and [Ca2+]i were increased to the same extent as when naive cells were treated with the A2 antagonist. Conversely, in cells where only A2 receptors were preserved, contraction and the increase in [Ca2+]i were abolished and the increase in cAMP was augmented to the same level as when naive cells were treated with the A1 antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adenosine A1 and A2b receptors coupled to distinct interactive signaling pathways in intestinal muscle cells. 761 13

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