Evidence of Direct Activation of Adenosine A1 Receptor by 5'-Adenosine Monophosphate in Isolated Guinea Pig Atrial Myocytes.

Wu, Sheng‐Nan; Lin, Yu-Cheng; Chen, Shun Sheng

doi:10.2170/jjphysiol.42.35

Cited by 7 publications

(9 citation statements)

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“…Direct activation of adenosine receptors by AMP has been shown previously [6], [7]. Therefore, experiments with different adenosine receptor antagonists were performed.…”

Section: Resultsmentioning

confidence: 91%

“…Previous studies were able to demonstrate that AMP can bind directly to A 1 receptors [6], [7]. Interestingly, A 1 receptor activation has been linked with intracellular Ca 2+ transients, actin polymerization, and migration in human monocytes-derived DCs [16], [17].…”

Section: Discussionmentioning

confidence: 97%

“…In the past, most of the effects elicited by AMP have been attributed to the fact that AMP can be degraded rapidly to adenosine. However, there is good evidence that AMP can also directly bind to A 1 and A 2A receptors without being dephosphorylated to adenosine before [6], [7]. In contrast, GPR80 (GPR99) which has been claimed to be a receptor specific for AMP has turned out to be a receptor for citric acid cycle intermediates but not for AMP [8], [9].…”

Section: Introductionmentioning

confidence: 99%

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AMP Affects Intracellular Ca2+ Signaling, Migration, Cytokine Secretion and T Cell Priming Capacity of Dendritic Cells

et al. 2012

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The nucleotide adenosine-5′-monophosphate (AMP) can be released by various cell types and has been shown to elicit different cellular responses. In the extracellular space AMP is dephosphorylated to the nucleoside adenosine which can then bind to adenosine receptors. However, it has been shown that AMP can also activate A1 and A2a receptors directly. Here we show that AMP is a potent modulator of mouse and human dendritic cell (DC) function. AMP increased intracellular Ca2+ concentration in a time and dose dependent manner. Furthermore, AMP stimulated actin-polymerization in human DCs and induced migration of immature human and bone marrow derived mouse DCs, both via direct activation of A1 receptors. AMP strongly inhibited secretion of TNF-α and IL-12p70, while it enhanced production of IL-10 both via activation of A2a receptors. Consequently, DCs matured in the presence of AMP and co-cultivated with naive CD4+CD45RA+ T cells inhibited IFN-γ production whereas secretion of IL-5 and IL-13 was up-regulated. An enhancement of Th2-driven immune response could also be observed when OVA-pulsed murine DCs were pretreated with AMP prior to co-culture with OVA-transgenic naïve OTII T cells. An effect due to the enzymatic degradation of AMP to adenosine could be ruled out, as AMP still elicited migration and changes in cytokine secretion in bone-marrow derived DCs generated from CD73-deficient animals and in human DCs pretreated with the ecto-nucleotidase inhibitor 5′-(alpha,beta-methylene) diphosphate (APCP). Finally, the influence of contaminating adenosine could be excluded, as AMP admixed with adenosine desaminase (ADA) was still able to influence DC function. In summary our data show that AMP when present during maturation is a potent regulator of dendritic cell function and point out the role for AMP in the pathogenesis of inflammatory disorders.

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“…Direct activation of adenosine receptors by AMP has been shown previously [6], [7]. Therefore, experiments with different adenosine receptor antagonists were performed.…”

Section: Resultsmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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AMP Affects Intracellular Ca2+ Signaling, Migration, Cytokine Secretion and T Cell Priming Capacity of Dendritic Cells

et al. 2012

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“…Suppression of norepinephrine release by an accumulation of AMP in the functioning intestine would be expected to remove sympathetic braking action from the neurons. This, together with AMP-evoked elevation of excitability in the neuronal cell bodies, is expected to enhance secretion of H 2 O, electrolytes and mucus and thereby increase the liquidity of the luminal contents, such as might occur in inflammatory states where ATP release is enhanced (8,10,11,16,18,19,22,25,39,44,51).…”

Section: Discussionmentioning

confidence: 99%

Stimulation of adenosine A₁and A_2Areceptors by AMP in the submucosal plexus of guinea pig small intestine

Gao¹,

Hu²,

Liu³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Actions of adenosine 5Ј-monophosphate (AMP) on electrical and synaptic behavior of submucosal neurons in guinea pig small intestine were studied with "sharp" intracellular microelectrodes. Application of AMP (0.3-100 M) evoked slowly activating depolarizing responses associated with increased excitability in 80.5% of the neurons. The responses were concentration dependent with an EC50 of 3.5 Ϯ 0.5 M. They were abolished by the adenosine A2A receptor antagonist ZM-241385 but not by pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid, trinitrophenyl-ATP, 8-cyclopentyl-1,3-dimethylxanthine, suramin, or MRS-12201220. The AMP-evoked responses were insensitive to AA-COCF3 or ryanodine. They were reduced significantly by 1) U-73122, which is a phospholipase C inhibitor; 2) cyclopiazonic acid, which blocks the Ca 2ϩ pump in intraneuronal membranes; and 3) 2-aminoethoxy-diphenylborane, which is an inositol (1,4,5)-trisphosphate receptor antagonist. Inhibitors of PKC or calmodulin-dependent protein kinase also suppressed the AMP-evoked excitatory responses. Exposure to AMP suppressed fast nicotinic ionotropic postsynaptic potentials, slow metabotropic excitatory postsynaptic potentials, and slow noradrenergic inhibitory postsynaptic potentials in the submucosal plexus. Inhibition of each form of synaptic transmission reflected action at presynaptic inhibitory adenosine A 1 receptors. Slow excitatory postsynaptic potentials, which were mediated by the release of ATP and stimulation of P2Y 1 purinergic receptors in the submucosal plexus, were not suppressed by AMP. The results suggest an excitatory action of AMP at adenosine A 2A receptors on neuronal cell bodies and presynaptic inhibitory actions mediated by adenosine A 1 receptors for most forms of neurotransmission in the submucosal plexus, with the exception of slow excitatory purinergic transmission mediated by the P2Y 1 receptor subtype. gastrointestinal tract; neurogastroenterology; enteric nervous system; synaptic transmission; purinergic receptors THE CELLULAR NEUROPHYSIOLOGY of purinergic receptors in the enteric nervous system (ENS), which encompasses both P1-and P2-type receptors, continues to be a focus of attention for neurogastroenterology. Adenosine is generally accepted as the ligand for the P1 receptor; ATP is the ligand for P2 receptors (1).P1 receptors are further classified as A 1 , A 2A , A 2B , and A 3 receptors according to their pharmacology, molecular sequences, and signal transduction pathways. Both A 2A and A 2B adenosine receptors are coupled through a G s protein to adenylate cyclase, elevation of cAMP, and stimulation of neuronal excitability. On the other hand, A 1 and A 3 adenosine receptors are negatively coupled to adenylate cyclase through the same G s protein (35, 43) and inhibit cAMP formation and neuronal excitability.In the ENS, adenosine acts as a presynaptic neuromodulator to influence the release of the inhibitory neurotransmitters norepinephrine and somatostatin (2, 53) and the excitatory neurotransmitters acetylcholine (ACh) and ...

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“…However, in atrial tissue, adenosine enhances activity of the acetylcholine-activated inward rectifier potassium current (I K(ACh) ). [18] The resulting shortening of atrial repolarization and effective refractory periods may promote reentry. [13, 19] In addition to its direct electrophysiological effects, adenosine may enhance adrenergic tone which may increase in the risk of AF.…”

Section: Cardiovascular Drugsmentioning

confidence: 99%

Drug-Induced Atrial Fibrillation

Kaakeh

Overholser

Lopshire

et al. 2012

Drugs

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Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with severe consequences, including symptoms, hemodynamic instability, increased cardiovascular mortality, and stroke. While other arrhythmias such as torsades de pointes and sinus bradycardia are more typically thought of as drug-induced, AF may also be precipitated by drug therapy, although ascribing causality to drug-associated AF is more difficult than with other drug-induced arrhythmias. Drug-induced AF is more likely to occur in patients with risk factors and comorbidities that commonly coexist with AF, such as advanced age, alcohol consumption, family history of AF, hypertension, thyroid dysfunction, sleep apnea, and heart disease. New-onset AF has been associated with cardiovascular drugs such as adenosine, dobutamine, and milrinone. In addition, medications such as corticosteroids, ondansetron, and antineoplastic agents such as paclitaxel, mitoxantrone, and anthracyclines have been reported to induce AF. Whether bisphosphonate drugs are associated with new onset AF remains controversial and requires further study. The potential contribution of specific drug therapy should be considered when patients present with new onset AF.

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Evidence of Direct Activation of Adenosine A1 Receptor by 5'-Adenosine Monophosphate in Isolated Guinea Pig Atrial Myocytes.

Cited by 7 publications

References 0 publications

AMP Affects Intracellular Ca2+ Signaling, Migration, Cytokine Secretion and T Cell Priming Capacity of Dendritic Cells

AMP Affects Intracellular Ca2+ Signaling, Migration, Cytokine Secretion and T Cell Priming Capacity of Dendritic Cells

Stimulation of adenosine A₁and A_2Areceptors by AMP in the submucosal plexus of guinea pig small intestine

Drug-Induced Atrial Fibrillation

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Evidence of Direct Activation of Adenosine A1 Receptor by 5'-Adenosine Monophosphate in Isolated Guinea Pig Atrial Myocytes.

Cited by 7 publications

References 0 publications

AMP Affects Intracellular Ca2+ Signaling, Migration, Cytokine Secretion and T Cell Priming Capacity of Dendritic Cells

AMP Affects Intracellular Ca2+ Signaling, Migration, Cytokine Secretion and T Cell Priming Capacity of Dendritic Cells

Stimulation of adenosine A1and A2Areceptors by AMP in the submucosal plexus of guinea pig small intestine

Drug-Induced Atrial Fibrillation

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Stimulation of adenosine A₁and A_2Areceptors by AMP in the submucosal plexus of guinea pig small intestine