Stimulation of nucleoside efflux and inhibition of adenosine kinase by A1 adenosine receptor activation

Sinclair, C. D.; Shepel, P. N.; Geiger, Jonathan D.; Parkinson, Fiona E.

doi:10.1016/s0006-2952(99)00350-0

Cited by 38 publications

(32 citation statements)

References 30 publications

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“…We have shown that synaptic transmission in knockout hippocampal slices is not inhibited, even by large quantities of adenosine (Johansson et al, 2001). However, information about the regulation and release of adenosine in this knockout model is important to obtain, and could help to resolve postulated mechanisms such as adenosine A 1 receptor-regulated adenosine release (Sinclair et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Mice lacking the adenosine A₁ receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly

Giménez-Llort

Masino

Diao

et al. 2005

Synapse

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Using mice with a targeted disruption of the adenosine A 1 receptor (A 1 R), we examined the role of A 1 Rs in hippocampal long-term potentiation (LTP), long-term depression (LTD), and memory formation. Recordings from the Shaffer collateral-CA1 pathway of hippocampal slices from adult mice showed no differences between theta burst and tetanic stimulation-induced LTP in adenosine A 1 receptor knockout (A 1 R −/− ), heterozygote (A 1 R +/− ), and wildtype (A 1 R +/+ ) mice. However, paired pulse facilitation was impaired significantly in A 1 R −/− slices as compared to (A 1 R +/+ ) slices. LTD in the CA1 region was unaffected by the genetic manipulation. The three genotypes showed similar memory acquisition patterns when assessed for spatial reference and working memory in the Morris water maze tasks at 9 months of age. However, 10 months later A 1 R −/− mice showed some deficits in the 6-arm radial tunnel maze test. The latter appeared, however, not due to memory deficits but to decreased habituation to the test environment. Taken together, we observe normal spatial learning and memory and hippocampal CA1 synaptic plasticity in adult adenosine A 1 R knockout mice, but find modifications in arousal-related processes, including habituation, in this knockout model.

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Section: Discussionmentioning

confidence: 99%

Mice lacking the adenosine A₁ receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly

Giménez-Llort

Masino

Diao

et al. 2005

Synapse

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“…Cyclohexyladenosine increases interstitial adenosine in metabolically stressed cells by a PKCdependent inhibition of adenosine kinase (57). Moreover, the adenosine kinase sequence has multiple PKC phosphorylation consensus sites (57).…”

Section: Discussionmentioning

confidence: 99%

Adenosine and opioid receptor-mediated cardioprotection in the rat: evidence for cross-talk between receptors

Peart

Gross

2003

American Journal of Physiology-Heart and Circulatory Physiology

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Peart, Jason N., and Garrett J. Gross. Adenosine and opioid receptor-mediated cardioprotection in the rat: evidence for cross-talk between receptors. Am J Physiol Heart Circ Physiol 285: H81-H89, 2003. First published March 13, 2003 10.1152/ajpheart.00985.2002The relative roles of free-radical production, mitochondrial ATP-sensitive K ϩ (mitoKATP) channels and possible receptor cross-talk in both opioid and adenosine A 1 receptor (A1AR) mediated protection were assessed in a rat model of myocardial infarction. Sprague-Dawley rats were subjected to 30 min of occlusion and 90 min of reperfusion. The untreated rats exhibited an infarct of 58.8 Ϯ 2.9% [infarct size (IS)/area at risk (AAR), %] at the end of reperfusion. Pretreatment with either the nonselective opioid receptor agonist morphine or the selective A1AR agonist 2-chloro-cyclopentyladenosine (CCPA) dramatically reduced IS/AAR to 41.1 Ϯ 2.2% and 37.9 Ϯ 5.5%, respectively (P Ͻ 0.05). Protection afforded by either morphine or CCPA was abolished by the reactive oxygen species scavenger N-(2-mercaptopropionyl)glycine or the mitoKATP channel blocker 5-hydroxydecanoate. Both morphine-and CCPA-mediated protection were attenuated by the selective A1AR antagonist 1,3-dipropyl-8-cyclopentylxanthine and the selective ␦ 1-opioid receptor (DOR) antagonist 7-benzylidenealtrexone. Simultaneous administration of morphine and CCPA failed to enhance the infarct-sparing effect of either agonist alone. These data suggest that both DOR and A 1AR-mediated cardioprotection are mitoK ATP and reactive oxygen species dependent. Furthermore, these data suggest that there are converging pathways and/or receptor cross-talk between A 1AR-and DOR-mediated cardioprotection.reactive oxygen species; ATP-sensitive potassium channel ADENOSINE AND ADENOSINE RECEPTOR agonists have been shown to protect the myocardium from ischemia-reperfusion injury (48-50). Earlier research focused on the role of the A 1 adenosine receptor (A 1 AR); however, recent evidence suggests that the A 3 adenosine receptor (A 3 AR) may also afford cardioprotection (29,48,50,63). Both A 1 AR and A 3 AR activation may be important triggers of both early preconditioning (EPC) and delayed preconditioning (DPC) (4, 58, 67); however, separate signaling pathways may be involved (38). Activation of opioid receptors has also been demonstrated to trigger EPC and DPC, primarily through the ␦-opioid receptor (DOR) (45,47,54). Indeed, blockade of the DOR abrogates the infarct-sparing effect of ischemic preconditioning (55).The signal-transduction pathways responsible for both DOR and A 1 /A 3 AR-mediated cardioprotection appear to be similar. A 1 ARs and A 3 ARs activate phospholipase C and phospholipase D, respectively (44). Activation of the DOR has also been reported to activate phospholipase C (33, 41). Activation of phospholipase C or phospholipase D results in translocation of specific isoforms of protein kinase C (PKC) (59, 61). Translocation of PKC may then lead to opening of a mitochondrial ATP-sensitive K ϩ (K ATP ) chan...

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“…For instance, it might directly block the effect of CHA in the spinal cord since theophylline readily crosses the blood-brain barrier. Alternatively (or additionally), theophylline might act by suppressing adenosinergic activation in peripheral tissues since IT CHA increases peripheral Ado levels (18,25). Therefore, it is possible that Ado receptor antagonists reverse the benefit of IT CHA by acting on neutrophils at the site of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Spinal adenosine receptor activation inhibits inflammation and joint destruction in rat adjuvant‐induced arthritis

Boyle

Moore

Yang

et al. 2002

Arthritis & Rheumatism

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Objective. To examine the effect of spinal cord adenosine (Ado) receptor stimulation on rat adjuvantinduced arthritis (AIA).Methods. Long-term intrathecal (IT) catheters were implanted into rats to provide spinal access for drug delivery. Animals were immunized with complete Freund's adjuvant at the tail base. Eight days later and every other day thereafter until day 20, rats were treated IT with the selective Ado A1 receptor agonist cyclohexyladenosine (CHA) or vehicle. In some experiments, animals received an additional daily intraperitoneal injection of the nonselective Ado antagonist theophylline. Paw swelling was measured by water displacement plethysmometry. The effect of IT CHA on the activation of activator protein 1 (AP-1) was determined by electromobility shift assay. Spinal cord c-Fos expression was determined by immunohistochemistry.Results. Spinal CHA significantly inhibited inflammation in AIA, with a mean ؎ SEM 20.9 ؎ 16.9% increase in paw swelling in the IT CHA group compared with 81.3 ؎ 10.6% in the saline group. The antiinflammatory effect of CHA was mediated through Ado receptors since the effect was reversed by coadministration of systemic theophylline. In addition, radiographs showed significantly less bone and cartilage destruction in the CHA-treated animals. Synovial expression of AP-1, which is a key regulator of metalloproteinase expression, was lower in IT CHA-treated animals. C-Fos expression was localized to spinal laminae I-VI, with a modest decrease observed in the superficial laminae in IT CHA-treated rats.Conclusion. These data demonstrate that the spinal cord can regulate peripheral inflammation. Therapeutic strategies that target the central nervous system might be useful in arthritis.The central nervous system (CNS) receives input from sites of peripheral inflammation and can, in turn, modulate the inflammatory process. For instance, inhibition of non-N-methyl-D-aspartate (NMDA) glutamate receptors in the lumbar dorsal horn suppresses knee swelling in rats after intraarticular injection with carrageenan. We have shown that spinal cord A1 adenosine (Ado) receptor agonists inhibit neutrophil accumulation in the skin of rats after intradermal injection with proinflammatory agents (1). In contrast to the knee edema model (2), this effect on neutrophil trafficking into peripheral sites is mediated by Ado-induced suppression of spinal NMDA receptor activation. The action of spinal cord Ado on neutrophil homing is independent of primary afferent fiber substance P and sympathetic neurons, but requires intact peripheral nerve connection since dorsal rhizotomy ablates the antiinflammatory activity (1).Understanding of the neural pathways and molecular mechanisms that process nociceptive information and subsequently regulate inflammatory peripheral responses is still in its formative stage. However, it is known that the spinal cord releases the excitatory amino acids glutamate and aspartate following nociceptive stimuli received via afferent C-fiber activation (3). Spinal cord neuronal re...

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Stimulation of nucleoside efflux and inhibition of adenosine kinase by A1 adenosine receptor activation

Cited by 38 publications

References 30 publications

Mice lacking the adenosine A₁ receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly

Mice lacking the adenosine A₁ receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly

Adenosine and opioid receptor-mediated cardioprotection in the rat: evidence for cross-talk between receptors

Spinal adenosine receptor activation inhibits inflammation and joint destruction in rat adjuvant‐induced arthritis

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Stimulation of nucleoside efflux and inhibition of adenosine kinase by A1 adenosine receptor activation

Cited by 38 publications

References 30 publications

Mice lacking the adenosine A1 receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly

Mice lacking the adenosine A1 receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly

Adenosine and opioid receptor-mediated cardioprotection in the rat: evidence for cross-talk between receptors

Spinal adenosine receptor activation inhibits inflammation and joint destruction in rat adjuvant‐induced arthritis

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Product

Resources

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Mice lacking the adenosine A₁ receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly

Mice lacking the adenosine A₁ receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly