Adenosine and adenosine receptors in immune function. Minireview and meeting report

Gilbertsen, Richard B.

doi:10.1007/bf01968823

Cited by 12 publications

(3 citation statements)

References 52 publications

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“…1). The A1 and A3 adenosine receptors coupled with Gi proteins are associated with two effector systems, namely, adenylate cyclase and phospholipase C. The binding of adenosine or its agonists to A1 and A3 adenosine receptors, either induce inhibition of adenylate cyclase leading to a decrease in intracellular cAMP levels or stimulate phospholipase C and the release of Ca 2+ (Gilbertsen, 1987; Soderback et al, 1991). The A 2A and A 2B receptors are associated with Gs proteins, their activation leading to an increase in intracellular cAMP (Abbracchio, 1996; Poulsen and Quinn, 1998).…”

Section: Adenosine: Metabolism Transport and Signal Transduction Mementioning

confidence: 99%

“…In the central nervous system, it acts as a neuroprotective agent via the suppression of neurotransmitter release and modulation of dopaminergic motor activity. Furthermore, it affects the immune system by exerting anti‐inflammatory activity through the inhibition of cytokine release and platelets aggregation, induction of erythropoietin production and modulation of lymphocyte function (Gilbertsen, 1987; Soderback et al, 1991; Phillis and O'Regan, 1993; Bouma et al, 1994; Von Lubitz et al, 1995; Lasely and Mentzer, 1996; Chen et al, 2000). This review focuses on the differential effect of adenosine or its agonists on the growth of tumor and normal cells, including the molecular mechanisms and specific receptor subtypes involved, with an emphasis on the role of the A3 adenosine receptor.…”

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confidence: 99%

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Differential effect of adenosine on tumor and normal cell growth: Focus on the A3 adenosine receptor

Ohana¹,

Bar-Yehuda²,

Barer³

et al. 2000

J. Cell. Physiol.

105

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Adenosine is an ubiquitous nucleoside present in all body cells. It is released from metabolically active or stressed cells and subsequently acts as a regulatory molecule through binding to speci®c A1, A 2A , A 2B and A3 cell surface receptors. The synthesis of agonists and antagonists to the adenosine receptors and their cloning enabled the exploration of their physiological functions. As nearly all cells express speci®c adenosine receptors, adenosine serves as a physiological regulator and acts as a cardioprotector, neuroprotector, chemoprotector, and as an immuno-modulator. At the cellular level, activation of the receptors by adenosine initiates signal transduction mechanisms through G-protein associated receptors. Adeno-sine's unique characteristic is to differentially modulate normal and transformed cell growth, depending upon its extracellular concentration, the expression of adenosine cell surface receptors, and the physiological state of the target cell. Stimulation of cell proliferation following incubation with adenosine has been demonstrated in a variety of normal cells in the range of low micromolar concentrations , including mesangial and thymocyte cells, Swiss mouse 3T3 ®bro-blasts, and bone marrow cells. Induction of apoptosis in tumor or normal cells was shown at higher adenosine concentrations (b100 mM) such as in leukemia HL-60, lymphoma U-937, A431 epidermoid cells, and GH3 tumor pituitary cell lines. It was further noted that the A3 adenosine receptor (A3AR) plays a key role in the inhibitory and stimulatory growth activities of adenosine. Modulation of the A3AR was found to affect cell growth either positively or negatively depending on the concentration of the agonist, similar to the effect described for adenosine. At nanomolar concentrations, the A3AR agonists possess dual activity, i.e., anti-proliferative activity toward tumor cells and stimulatory effect on bone marrow cells. In vivo, these agonists exerted anti-cancer effects, and when given in combination with chemotherapy, they enhanced the chemotherapeutic index and acted as chemoprotective agents. Taken together, activation of the A3AR, by minute concentrations of its natural ligand or synthetic agonists, may serve as a new approach for cancer therapy.

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Section: Adenosine: Metabolism Transport and Signal Transduction Mementioning

confidence: 99%

mentioning

confidence: 99%

Differential effect of adenosine on tumor and normal cell growth: Focus on the A3 adenosine receptor

Ohana¹,

Bar-Yehuda²,

Barer³

et al. 2000

J. Cell. Physiol.

105

View full text Add to dashboard Cite

show abstract

“…Since specific surface receptors for adenosine are found in nearly all cells, almost every organ system in the body is regulated by its local release, that is, regulation of the electrophysiological properties of the heart, sedation and suppression of neurotransmitters' release, and regulation of renin release as well as vascular tone in the kidney (Belardinelli et al, 1989;Clarke and Coupe, 1989;Collis, 1989;Dubey et al, 1997). Adenosine exerts various effects on the immune system including anti-inflammatory activity through the inhibition of cytokine release, inhibition of platelet aggregation, induction of erythropoietin production, and modulation of the lymphocyte function (Gilbertsen, 1987;Soderback et al, 1991;Bouma et al, 1994).…”

mentioning

confidence: 99%

Adenosine acts as a chemoprotective agent by stimulating G-CSF production: A role for A1 and A3 adenosine receptors

et al. 2000

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Adenosine, a ubiquitous nucleoside, is released into the extracellular environment from metabolically active or stressed cells. It binds to cells through specific A1, A(2A), A(2B), and A3 G-protein-associated cell-surface receptors, thus acting as a signal-transduction molecule by regulating the levels of adenylyl cyclase and phospholipase C. In this study, we showed that adenosine stimulates the proliferation of murine bone marrow cells in vitro. Pharmacological studies, using antagonists to the adenosine receptors, revealed that this activity was mediated through the binding of adenosine to its A1 and A3 receptors. This result was further corroborated by showing that the two selective A1 and A3 receptor agonists, N-cyclopentyladenosine (CPA) and 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-be ta-D-ribofuranuronamide (IB-MECA) respectively, induced bone marrow cell proliferation in a manner similar to adenosine. Adenosine's interaction with its A1 and A3 receptors induced G-CSF production, which led to its stimulatory effect on bone marrow cells. These results were confirmed in vivo when we demonstrated that low-dose adenosine (0.25 mg/kg) acted as a chemoprotective agent. When administered after chemotherapy, it restored the number of leukocytes and neutrophils to normal levels, compared with the decline in these parameters after chemotherapy alone. It is suggested that low-dose adenosine, already in clinical use, may also be applied as a chemoprotective agent.

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CD26/DPIV in Hematopoietic Cells — Expression, Function, Regulation, Clinical Aspects

et al. 2002

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Adenosine and adenosine receptors in immune function. Minireview and meeting report

Cited by 12 publications

References 52 publications

Differential effect of adenosine on tumor and normal cell growth: Focus on the A3 adenosine receptor

Differential effect of adenosine on tumor and normal cell growth: Focus on the A3 adenosine receptor

Adenosine acts as a chemoprotective agent by stimulating G-CSF production: A role for A1 and A3 adenosine receptors

CD26/DPIV in Hematopoietic Cells — Expression, Function, Regulation, Clinical Aspects

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