Adenosine receptors as potential therapeutic targets

Kaiser, Sonya M.; Quinn, Ronald J.

doi:10.1016/s1359-6446(99)01421-x

Cited by 51 publications

(36 citation statements)

References 85 publications

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“…These results contribute to identify the neutrophil as an important effector for A 2A R-derived anti-inflammatory signaling. In support of this, activation of the A 2A R has been Journal of Cell Science 118 (7) shown to centrally mediate the downregulatory impact of adenosine on many of the neutrophil's cytotoxic functions, including the expression of β2-integrins, adhesion, oxygen radical production, degranulation and production of TNF-α (reviewed by Kaiser and Quinn, 1999;Thiel et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…In particular, A 2A R have been identified as being part of a a nonredundant signaling system in attenuating inflammation and tissue damage; no other mechanism of downregulation of inflammation in vivo appears able to fully compensate for the lack of A 2A R; this was clearly shown with mice deficient in the A 2A R, which developed extensive tissue damage in response to subthreshold concentrations of inflammatory stimuli (Ohta and Sitkovsky, 2001). Accordingly, there is clinical interest for the use of adenosine and its analogues in the treatment of inflammatory diseases such as arthritis and asthma, as well as for more general processes such as wound healing, and this interest stresses the need for a better understanding of the downstream events triggered by anti-inflammatory A 2A R agonists (for a review, see Kaiser and Quinn, 1999).…”

Section: Discussionmentioning

confidence: 99%

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Potentiation of neutrophil cyclooxygenase-2 by adenosine: an early anti-inflammatory signal

Cadieux

Leclerc

St-Onge

et al. 2005

Journal of Cell Science

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Neutrophils, which are often the first to migrate at inflamed sites, can generate leukotriene B4 from the 5-lipoxygenase pathway and prostaglandin E2 through the inducible cyclooxygenase-2 pathway. Adenosine, an endogenous autacoid with several anti-inflammatory properties, blocks the synthesis of leukotriene B4 while it potentiates the cyclooxygenase-2 pathway in fMLP-treated neutrophils, following activation of the A2A receptor. Using the murine air pouch model of inflammation, we observed that inflammatory leukocytes from mice lacking the A2A receptor have less cyclooxygenase-2 induction than wild-type animals. In human leukocytes, A2A receptor activation specifically elicited potentiation of cyclooxygenase-2 in neutrophils, but not in monocytes. Signal transduction studies indicated that the cAMP, ERK1/2, PI-3K and p38K intracellular pathways are implicated both in the direct upregulation of cyclooxygenase-2 and in its potentiation. Together, these results indicate that neutrophils are particularly important mediators of adenosine's effects. Given the uncontrolled inflammatory phenotype observed in knockout mice and in view of the potent inhibitory actions of prostaglandin E2 on inflammatory cells, an increased cyclooxygenase-2 expression resulting from A2A receptor activation, observed particularly in neutrophils, may take part in an early modulatory mechanism promoting anti-inflammatory activities of adenosine.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Potentiation of neutrophil cyclooxygenase-2 by adenosine: an early anti-inflammatory signal

Cadieux

Leclerc

St-Onge

et al. 2005

Journal of Cell Science

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“…In addition to maintenance of sodium homeostasis under physiological conditions, a rise in adenosine after renal ischemia has protective effects against renal cell damage via a multitude of intrarenal and extrarenal mechanisms (2,(61)(62)(63). Regulation of NHE3 activity by adenosine may represent a versatile mechanism to adapt the energy supply/demand balance of the proximal tubule under physiological as well as certain pathophysiological conditions.…”

Section: Discussionmentioning

confidence: 99%

Acute Regulation of Na/H Exchanger NHE3 by Adenosine A1 Receptors Is Mediated by Calcineurin Homologous Protein

Sole

Cerull

Babich

et al. 2004

Journal of Biological Chemistry

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“…There is increasing interest in the therapeutic potential of purinergic compounds in a wide range of diseases, in relation to both P1 receptors [16][17][18][19] and P2 receptors [12][13][14]20 . A number of purine-related compounds have been patented 21 .…”

Section: Pathophysiology and Therapeutic Developmentsmentioning

confidence: 99%

Potential therapeutic targets in the rapidly expanding field of purinergic signalling

Burnstock

2002

Clinical Medicine

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-The concept of a purinergic signalling system, using purine nucleotides and nucleosides as extracellular messengers, was first proposed over 30 years ago. After a brief historical review and update of purinoceptor subtypes, this article focuses on the diverse physiological roles of adenosine triphosphate, adenosine diphosphate, uridine triphosphate and adenosine. These molecules mediate short-term (acute) signalling functions in neurotransmission, secretion and vasodilation, and long-term (chronic) signalling functions in development, regeneration, proliferation and cell death. Plasticity of purinoceptor expression in pathological conditions is frequently obser ved, including an increase in the purinergic component of parasympathetic nervous control of the human bladder in interstitial cystitis and outflow obstruction, and in sympathetic cotransmitter control of blood vessels in hypertensive rats. The antithrombotic action of clopidogrel (Plavix), a P2Y 12 receptor antagonist, has been shown to be particularly promising in the prevention of recurrent strokes and heart attacks in recent clinical trials (CAPRIE and CURE). The role of P2X 3 receptors in nociception and a new hypothesis concerning purinergic mechanosensory transduction in visceral pain will be considered, as will the therapeutic potential of purinergic agonists or antagonists for the treatment of supraventricular tachycardia, cancer, dry eye, bladder hyperactivity, erectile dysfunction, osteoporosis, diabetes, gut motility and vascular disorders. KEY WORDS: purinoceptors, interstitial cystitis, thrombosis, visceral pain, cancer, osteoporosis, peripheral vascular disease, cystic fibrosis, Parkinson' s disease, kidney failure Purinergic signalling: history and receptor subtypes A seminal paper by Drury and Szent-Györgi in 1929 described the potent actions of purine nucleotides and nucleosides, adenosine triphosphate (ATP) and adenosine on the heart and blood vessels 1 . A landmark paper by Pamela Holton in 1959 showed that, during antidromic stimulation of sensory nerves, ATP was released to the rabbit ear artery in sufficient amounts to produce changes in vascular tone 2 . Then, in 1970, Burnstock et al. found evidence for the role of ATP as a neurotransmitter in nonadrenergic, noncholinergic (NANC) nerves supplying the gut 3 , and, in 1972, the word 'purinergic' was coined and the purinergic-neurotransmission hypothesis was put forward 4 (Fig 1). This concept met with considerable resistance for many years because ATP had been established as an intracellular energy source involved in various metabolic cycles, and it was thought that such a ubiquitous molecule was unlikely to be involved in selective extracellular signalling. However, the concept is now widely accepted. Later, it was established that ATP is a cotransmitter with classical transmitters in both the peripheral and the central nervous systems, and that purines are powerful extracellular messengers to non-neuronal cells, including exocrine and endocrine, secretory, endothelial, b...

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Adenosine receptors as potential therapeutic targets

Cited by 51 publications

References 85 publications

Potentiation of neutrophil cyclooxygenase-2 by adenosine: an early anti-inflammatory signal

Potentiation of neutrophil cyclooxygenase-2 by adenosine: an early anti-inflammatory signal

Acute Regulation of Na/H Exchanger NHE3 by Adenosine A1 Receptors Is Mediated by Calcineurin Homologous Protein

Potential therapeutic targets in the rapidly expanding field of purinergic signalling

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