Signalling from adenosine receptors to mitogen-activated protein kinases

Schulte, Gunnar; Fredholm, Bertil B.

doi:10.1016/s0898-6568(03)00058-5

Cited by 428 publications

(369 citation statements)

References 207 publications

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“…In addition to classical cAMP-mediated pathways, evidence is accumulating for P1 receptors operating through alternative signaling systems. Of particular note, evidence for protein kinase C (PKC), phosphoinositide 3 kinase (PI3K) kinase and mitogen activated protein kinase (MAPK) involvement in P1-mediated signaling cascades have been reported (Schulte and Fredholm, 2003). Further, the direct activation of K þ channels and inhibition of Ca 2þ channels has been reported following A 1 receptor activation (Hasko and Pacher, 2008).…”

Section: The Role Of Adenosine In Neuroinflammationmentioning

confidence: 99%

Purinergic mechanisms in neuroinflammation: An update from molecules to behavior

et al. 2016

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a b s t r a c tThe principle functions of neuroinflammation are to limit tissue damage and promote tissue repair in response to pathogens or injury. While neuroinflammation has utility, pathophysiological inflammatory responses, to some extent, underlie almost all neuropathology. Understanding the mechanisms that control the three stages of inflammation (initiation, propagation and resolution) is therefore of critical importance for developing treatments for diseases of the central nervous system. The purinergic signaling system, involving adenosine, ATP and other purines, plus a host of P1 and P2 receptor subtypes, controls inflammatory responses in complex ways. Activation of the inflammasome, leading to release of pro-inflammatory cytokines, activation and migration of microglia and altered astroglial function are key regulators of the neuroinflammatory response. Here, we review the role of P1 and P2 receptors in mediating these processes and examine their contribution to disorders of the nervous system. Firstly, we give an overview of the concept of neuroinflammation. We then discuss the contribution of P2X, P2Y and P1 receptors to the underlying processes, including a discussion of cross-talk between these different pathways. Finally, we give an overview of the current understanding of purinergic contributions to neuroinflammation in the context of specific disorders of the central nervous system, with special emphasis on neuropsychiatric disorders, characterized by chronic low grade inflammation or maternal inflammation. An understanding of the important purinergic contribution to neuroinflammation underlying neuropathology is likely to be a necessary step towards the development of effective interventions.

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Section: The Role Of Adenosine In Neuroinflammationmentioning

confidence: 99%

Purinergic mechanisms in neuroinflammation: An update from molecules to behavior

et al. 2016

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“…The cardiovascular effects of A 2B AR were found to be similar to A 2A AR but it is a low affinity AR [13][14][15]. It has been speculated that under pathological conditions, such as ischemia, A 2B AR may be up-regulated to compensate for the down-regulation of A 2A AR-mediated responses.…”

Section: Introductionmentioning

confidence: 99%

Up-regulation of A2B adenosine receptor in A2A adenosine receptor knockout mouse coronary artery

Teng¹,

Ledent²,

Mustafa³

2008

Journal of Molecular and Cellular Cardiology

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In this study, we looked into possible compensatory changes of other adenosine receptors (AR) in A 2A genetic knockout mice (A2AKO) as well as the functional role of nitric oxide (NO) in A 2A ARmediated vasodilation. Gene expression of ARs from coronary arteries of A 2A AR wild type mice (A2AWT) and A2AKO were studied using real time-PCR. Functional studies were carried out in isolated heart and isolated coronary artery preparations. A 2B AR was found to be 4.5 fold higher in A2AKO than in A2AWT, while A 2A AR expression was absent in A2AKO. There was no difference in A 1 and A 3 ARs between WT and KO animals. The concentration-relaxation curve for adenosine-5′-N-ethylcarboxamide (NECA, non-selective AR agonist) in isolated coronary arterial rings in A2AKO was shifted to the left when compared to A2AWT. The concentration-response curve for A 2B selective agonist (Bay 60-6583) was also shifted to the left in A2AKO hearts. L-NAME, a nonspecific NO synthase inhibitor, did not affect baseline coronary flow (CF) until the concentration reached 10 µM in A 2A WT (76.32 ± 11.35% from baseline, n=5). In A 2A KO, the CF decreased significantly by L-NAME only at a higher concentration (100 µM, 93.32 ± 5.8% from baseline, n=5). L-NMA (1 µM, n=4), another non-specific NO synthase inhibitor, also demonstrated similar results in decreasing CF (59.66±3.23% from baseline in A2AWT, while 81.76±8.91% in A2AKO). It was further demonstrated that the increase in CF by 100 µM NECA was significantly blunted with 10 µM L-NAME (377.08 ± 25.23% to 305.41 ± 30.73%, n=9) in A 2A WT but not in A 2A KO (153.66 ± 22.7% to 143.88 ± 36.65%, n=5). Similar results were also found using 50 nM of CGS-21680 instead of NECA in A 2A WT (346±22.85 to 277±31.39, n=6). No change in CF to CGS-21680 was noted in A 2A AKO. Our data demonstrate, for the first time, that coronary A 2B AR was up-regulated in mice deficient in A 2A AR. We also provide direct evidence supporting a role for NO in A 2A AR-mediated coronary vasodilation. The data further support the role for A 2A AR in the regulation of basal coronary tone through the release of NO.

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“…The relaxation to ADP in our study was largely reduced in the presence of XAC and SCH58261 (adenosine receptor antagonists). Adenosine receptors may be expressed on the endothelium or the vascular smooth muscle [42]. Since XAC and SCH58261 produced a greater reduction in the relaxation to ADP than the inhibition induced by removal of the endothelium (Fig.…”

Section: Discussionmentioning

confidence: 99%

Investigation of the functional expression of purine and pyrimidine receptors in porcine isolated pancreatic arteries

Alsaqati

Chan

Ralevic

2013

Purinergic Signalling

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Receptors for purines and pyrimidines are expressed throughout the cardiovascular system. This study investigated their functional expression in porcine isolated pancreatic arteries. Pancreatic arteries (endothelium intact or denuded) were prepared for isometric tension recording and preconstricted with U46619, a thromboxane A 2 mimetic; adenosine-5′-diphosphate (ADP), uridine-5′-triphosphate (UTP) and MRS2768, a selective P2Y 2 agonist, were applied cumulatively, while adenosine-5′-triphosphate (ATP) and αβ-methylene-ATP (αβ-meATP) response curves were generated from single concentrations per tissue segment. Antagonists/ enzyme inhibitors were applied prior to U46619 addition. ATP, αβ-meATP, UTP and MRS2768 induced vasoconstriction, with a potency order of αβ-meATP > MRS2768 > ATP ≥ UTP. Contractions to ATP and αβ-meATP were blocked by NF449, a selective P2X1 receptor antagonist. The contraction induced by ATP, but not UTP, was followed by vasorelaxation. Endothelium removal and DUP 697, a cyclooxygenase-2 inhibitor, had no significant effect on contraction to ATP but attenuated that to UTP, indicating actions at distinct receptors. MRS2578, a selective P2Y 6 receptor antagonist, had no effect on contractions to UTP. ADP induced endothelium-dependent vasorelaxation which was inhibited by MRS2179, a selective P2Y 1 receptor antagonist, or SCH58261, a selective adenosine A 2A receptor antagonist. The contractions to ATP and αβ-meATP were attributed to actions at P2X1 receptors on the vascular smooth muscle, whereas it was shown for the first time that UTP induced an endothelium-dependent vasoconstriction which may involve P2Y 2 and/or P2Y 4 receptors. The relaxation induced by ADP is mediated by P2Y 1 and A 2A adenosine receptors. Porcine pancreatic arteries appear to lack vasorelaxant P2Y 2 and P2Y 4 receptors.

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Signalling from adenosine receptors to mitogen-activated protein kinases

Cited by 428 publications

References 207 publications

Purinergic mechanisms in neuroinflammation: An update from molecules to behavior

Purinergic mechanisms in neuroinflammation: An update from molecules to behavior

Up-regulation of A2B adenosine receptor in A2A adenosine receptor knockout mouse coronary artery

Investigation of the functional expression of purine and pyrimidine receptors in porcine isolated pancreatic arteries

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