Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Quantitative and qualitative changes in adrenoceptors under various conditions were studied by binding experiments. Chronic treatment with reserpine increased the level of alpha 2-adrenoceptors in rat vas deferens and hypoxia increased the level of alpha 1-adrenoceptors in rat cardiomyocytes. Adenosine receptor agonists increased the affinity of the alpha 2-adrenoceptor in rat vas deferens for the agonist with an increase in receptor-mediated responses. Thus two types of changes in receptor binding sites were observed. Next, changes in the GTP-binding (G) protein were studied. Activation of cyclic AMP-dependent protein kinase (PKA) decreased the ADP-ribosylation of Gi (41 K) protein by islet-activating protein (pertussis toxin, IAP). Purified Gi protein was phosphorylated by the enzyme. IAP-sensitive G protein-mediated coupling responses such as phosphatidylinositol turnover in differentiated HL-60 cells were also modified under this condition. These results indicated that phosphorylation of Gi by PKA caused a qualitative change of Gi. Lithium ions also decreased the ADP-ribosylation of Gi by IAP. Then it determined if the decrease was accompanied with a dissociation of the subunits of Gi. Phosphorylation of Gi by PKA impaired the dissociation of the subunits of Gi caused by Mg2+ and GTP gamma S, whereas lithium ions did not have any effect on their dissociation. Thus some conditions caused a functional change in the so-called "qualitative change" of Gi.
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PMID:The mechanism of changes in adrenoceptor-mediated responses. 217 4

Adenosine receptors of the A1 and A2 subtypes were characterized in membranes from DDT1 MF-2 smooth muscle cells. These cells possess a high density of A1 adenosine receptors (Bmax = 0.8-0.9 pmol/mg of protein), as measured by both agonist and antagonist radioligands. Agonists compete for [125I]N6-[2-(4-amino-3-iodophenyl)ethyl]-adenosine (A1 receptor-selective radioligand) binding with the following potency series: (R)-phenylisopropyladenosine [(R)-PIA] greater than 5'-N-ethylcarboxamide adenosine (NECA) greater than (S)-PIA, indicative of their interaction with A1 adenosine receptors. Agonist competition for [3H]8-(4-[[[(2-aminoethyl)amino]carbonyl)methyl)oxy]phenyl)-1, 3-dipropylxanthine [( 3H]XAC) (an antagonist radioligand for the A1 adenosine receptor) was described by a two-state model of 1.3 nM (high affinity state, KK) and 370 nM (low affinity state, KL), with 70% of the receptors in the high affinity state (RH). Addition of guanosine 5'-[beta, alpha-imido]triphosphate (100 microM) shifted the (R)-PIA competition curves to the right to lower affinities. Photoaffinity labeling with the agonist photoprobe [125I]N6-[2-(4-amino-3-iodophenyl) ethyl]adenosine indicates that the A1 adenosine receptor binding subunit is a Mr 38,000 protein. Adenosine receptor agonists [(R)-PIA, NECA, and (S)-PIA] inhibited isoproterenol-stimulated adenylate cyclase activity in DDT1 MF-2 cell membranes with IC50 values of 62, 538, and 750 nM, respectively. Inhibition of adenylate cyclase by (R)-PIA was attenuated by the A1 receptor antagonist XAC and following inactivation of Gi with pertussis toxin (100 ng/ml). Using a recently developed A2 adenosine receptor agonist radioligand 2-[4-(2-[( 4-aminophenyl]methylcarbonyl)ethyl) phenyl]ethylamino-5'-N-ethylcarboxamido adenosine (125I-PAPA-APEC), we have demonstrated the presence of A2 adenosine receptors in this cell line. Saturation curves with 125I-PAPA-APEC indicated the Bmax and Kd values to be 0.21 pmol/mg of protein and 4.0 nM, respectively. In competition experiments, NECA was more potent at inhibiting 125I-PAPA-APEC binding than (R)-PIA, with their respective IC50 values being 5.6 and 351 nM. The photolabeled A2 adenosine receptor migrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an Mr of 42,000. Finally, adenosine receptor agonists stimulated adenylate cyclase activity by approximately 2-3 fold with the following potency series: PAPA-APEC greater than or equal to NECA greater than (R)-PIA, indicative of their interaction at A2 receptors. These data represent the first demonstration of the presence of both A1 and A2 receptors in a single cell line, DDT1 MF-2 smooth muscle cells.
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PMID:Demonstration of both A1 and A2 adenosine receptors in DDT1 MF-2 smooth muscle cells. 230 50

An adenosine receptor has been characterized to unambiguously demonstrate that the inhibitory guanine nucleotide regulatory protein, Gi, of 1321N1 human astrocytoma cells is fully capable of functionally coupling to adenylate cyclase. Adenosine receptor agonists attenuated cyclic AMP accumulation by 35 to 75% with the order of potency of N6(R-phenylisopropyl)-adenosine greater than adenosine = 2-chloroadenosine greater than N6-methyladenosine = N6-benzyladenosine. 3-Isobutyl-1-methylxanthine competitively antagonized the effect of adenosine receptor agonists. Adenylate cyclase activity measured in cell-free preparations from 1321N1 cells was inhibited by N6(R-phenylisopropyl)-adenosine. Pretreatment of 1321N1 cells with pertussis toxin blocked both adenosine receptor-mediated inhibition of adenylate cyclase activity and attenuation of cyclic AMP accumulation. In contrast to the effects on responses to adenosine receptor agonists, 3-isobutyl-1-methylxanthine noncompetitively antagonized muscarinic receptor-mediated attenuation of cyclic AMP accumulation and pertussis toxin had no effect. These data are consistent with the ideas that Gi is fully functional in 1321N1 cells and links inhibitory adenosine receptors to adenylate cyclase, and that the muscarinic receptor of these cells couples to the phosphoinositide response system, but is incapable of functionally coupling through Gi to inhibit adenylate cyclase.
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PMID:Adenosine and muscarinic cholinergic receptors attenuate cyclic AMP accumulation by different mechanisms in 1321N1 astrocytoma cells. 242 Sep 67

Adenosine analogs were used to investigate the cellular mechanisms by which adenosine may alter renal tubular function. Cultured rabbit cortical collecting tubule (RCCT) cells, isolated by immunodissection, were treated with 5'-N-ethylcarboxamideadenosine (NECA), N6-cyclohexyladenosine (CHA), and R-N6-phenylisopropyladenosine (PIA). All three analogs produced both dose-dependent inhibition and stimulation of RCCT cell cyclic AMP (cAMP) production. Stimulation of cAMP accumulation occurred at analog concentrations of 0.1 microM to 100 microM with the rank order of potency NECA greater than PIA greater than CHA. Inhibition occurred at concentrations of 1 nM to 1 microM with the rank order of potency CHA greater than PIA greater than NECA. These effects on cAMP production were inhibited by 1,3-diethyl-8-phenylxanthine and isobutylmethylxanthine. CHA (50 nM) blunted AVP- and isoproterenol-stimulated cAMP accumulation. This modulation of hormone-induced cAMP production was abolished by pretreatment of RCCT cells with pertussis toxin. Prostaglandin E2 production was unaffected by 0.1 mM CHA. These findings indicate the presence of both inhibitory (A1) and stimulatory (A2) receptors for adenosine in RCCT cells. Moreover, occupancy of the A1 receptor causes inhibition of both basal and hormone-stimulated cAMP formation through an action on the inhibitory guanine nucleotide-binding regulatory component, Ni, of the adenylate cyclase system.
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PMID:A1 and A2 adenosine receptors in rabbit cortical collecting tubule cells. Modulation of hormone-stimulated cAMP. 243 28

Adenosine has a negative inotropic effect in cardiac atrial preparations ("direct" negative inotropic effect). This effect is probably due to an activation of a potassium outward current which shortens the action potential duration and hence reduces the force of contraction. A pertussis toxin-sensitive N-protein is involved in the signal transduction from the adenosine receptor to atrial potassium channels. In ventricular cardiac preparations adenosine has no negative or even a weak positive inotropic effect, but it reduces the force of contraction in the presence of cAMP-increasing agents such as isoprenaline ("indirect" negative intropic effect). This effect is due to an inhibition of the slow Ca2+ inward current which has previously been enhanced by an increase in the cellular cAMP content. This "indirect" negative inotropic effect of adenosine is also present in the human heart. Since increased amounts of adenosine are released during cardiac stimulation via beta-adrenoceptors, the "indirect" effect might protect the heart against excessive stimulation by catecholamines. In addition, adenosine has negative chronotropic actions and prolongs AV conduction by an activation of potassium channels or an inhibition of the slow Ca2+ inward current (AV node). Cardiac bradyarrhythmias in hypoxia have been attributed to an increased formation and release of adenosine. Furthermore, adenosine has been shown to terminate supraventricular tachycardias involving the AV node. Since it has a very short duration of action it might prove safe and hence advantageous to conventional therapy in the treatment of supraventricular tachycardias.
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PMID:[Cardiac effects of adenosine. Mechanism of action, pathophysiologic and clinical significance]. 244 Nov 9

Adenosine analogues selective for the A1 subclass of adenosine receptors, such as N6-cyclohexyladenosine (CHA), induce vasoconstriction in the isolated rat kidney perfused at constant flow. Presumably, the vasoconstriction is mediated by increased Ca2+ concentration in renal vascular smooth muscle cells, but the mechanism by which A1 adenosine receptor occupation leads to increased Ca2+ is unknown. In the present experiments, the isolated, perfused rat kidney vasoconstricted in response to CHA, to K depolarization, and to BAY K 8644 (a Ca2+ channel agonist). All of these responses were completely blocked by methoxyverapamil, which suggests that CHA, like K depolarization and BAY K 8644, induces renal vasoconstriction by increasing Ca2+ influx through potential operated Ca2+ channels. The mechanism of action of CHA was different, however, in that pertussis toxin treatment blocked the response to CHA without affecting the responses to K depolarization or to BAY K 8644. Therefore, a pertussis toxin-sensitive step must intervene between occupation of A1 adenosine receptors on renal vascular smooth muscle cells and increased Ca2+ influx through potential-operated Ca2+ channels.
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PMID:Mechanism of adenosine receptor-induced renal vasoconstriction in rats. 245 75

Adenosine exerts prominent inhibitory effects on synaptic transmission via a presynaptic action. Using the hippocampal slice preparation, we have found in electrophysiological experiments that this action of adenosine is blocked by intrahippocampal injections of pertussis toxin. In biochemical studies, we have confirmed that this treatment affects the GTP-binding proteins, Gi and Go, in this preparation. These results indicate that both pre- and postsynaptic actions of adenosine involve pertussis toxin-sensitive GTP-binding proteins.
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PMID:Intrahippocampal injection of pertussis toxin blocks adenosine suppression of synaptic responses. 250 87

Norepinephrine (NE) stimulated FRTL-5 thyroid cells via an alpha 1-adrenergic receptor, resulting in cytosolic Ca2+ [( Ca2+]i) mobilization and activation of phospholipase C. Adenosine and its receptor agonist, phenylisopropyladenosine (PIA), although not exerting a direct effect, markedly enhanced the NE-induced changes. Basal NE action was not totally abolished whereas the permissive action of adenosine and PIA was completely abolished by pretreatment of the cells with islet-activating protein (IAP), pertussis toxin. The decrease in cAMP level induced by adenosine or PIA is not the cause of their permissive effect, since the effect was not reversed by the addition of cAMP-increasing agents. We conclude that an IAP substrate GTP-binding protein(s) plays a novel role in forming a stimulatory coupling between an adenosine receptor and an alpha 1-adrenergic receptor-coupled phospholipase C system.
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PMID:Stimulation of adenosine receptor enhances alpha 1-adrenergic receptor-mediated activation of phospholipase C and Ca2+ mobilization in a pertussis toxin-sensitive manner in FRTL-5 thyroid cells. 254 83

Extracellular ATP and other purinergic agonists were found to inhibit cAMP accumulation by depressing adenylate cyclase as an "inhibitory action" and/or to stimulate arachidonate release in association with phospholipase C or A2 activation and Ca2+ mobilization as "stimulatory actions" in FRTL-5 cells. The stimulatory actions of a group of P2-agonists represented by ATP were partially inhibited by the pretreatment of the cells with islet-activating protein (IAP), pertussis toxin, even when an about 41-kDa membrane protein(s) was completely ADP-ribosylated. Only the IAP-sensitive part of the stimulatory actions was antagonized by 1,3-diethyl-8-phenylxanthine (DPX), an adenosine antagonist. GTP and 8-bromoadenosine 5'-triphosphate (Br-ATP) at two to three orders of higher concentrations than ATP also exerted the stimulatory actions, although they were entirely insensitive to both IAP and DPX. Ligand binding experiments with, [35S]ATP gamma S and [3H]DPX showed that ATP occupies both DPX-sensitive and insensitive receptor sites, whereas GTP does only ATP-displaceable DPX-insensitive sites. Thus, lack of sensitivity of GTP action to DPX was associated with its inability to occupy the DPX-sensitive sites. Adenosine 5'-O-(1-thiotriphosphate) (ATP alpha S), adenosine 5'-O-(2-thiodiphosphate) (ADP beta S) and P1-agonists such as AMP and N6-(L-2-phenylisopropyl-adenosine (PIA) did not show any stimulatory action. Nevertheless, the agonists remarkably enhanced the stimulatory actions of GTP or Br-ATP. Such permissive actions of PIA and others were sensitive to both IAP and DPX, as were shown for a part of the stimulatory actions of ATP as well as the "inhibitory actions" of both PIA and ATP. We conclude that an IAP substrate G-protein(s) which mediates the inhibitory action of purinergic agonists via a DPX-sensitive purinergic receptor(s) may not directly link to the phospholipase C or A2 system but enhance the system which links to a DPX-insensitive P2-receptor, in an indirect or permissive manner.
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PMID:A permissive role of pertussis toxin substrate G-protein in P2-purinergic stimulation of phosphoinositide turnover and arachidonate release in FRTL-5 thyroid cells. Cooperative mechanism of signal transduction systems. 254 44

The present study has examined the effects of adenosine A1 receptors on second messenger processes in GH3 cells. A1 receptors are present which are shown to inhibit adenylate cyclase in a GTP-requiring manner. Hormone (VIP) stimulation is also absolutely required for the observation of inhibition. Adenosine A1 receptor analogues also inhibit TRH-stimulated [Ca2+]i-mobilization in GH3 cells. Both effects of the adenosine receptor agonists are apparently mediated by pertussis toxin substrates, of which there are two--41,000 and 40,000 daltons respectively--in these cells. Somatostatin exerts analogous effects to the adenosine agonists in GH3 cells. Thus it may turn out that a general property of 'cyclase inhibitory receptors' is also to inhibit [Ca2+]i-mobilization in the same cells, when such mechanisms are present.
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PMID:Adenosine A1 receptors inhibit both adenylate cyclase activity and TRH-activated Ca2+ channels by a pertussis toxin-sensitive mechanism in GH3 cells. 257 20


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