Adenosine receptors: new opportunities for future drugs

Poulsen, Sally‐Ann; Quinn, Ronald J.

doi:10.1016/s0968-0896(98)00038-8

Cited by 278 publications

(243 citation statements)

References 131 publications

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“…From this result and the present findings that CPA antagonizes dopamine-induced inhibition of NHE3, a role of adenosine in Na ϩ homeostasis may be that of a direct and indirect modulator of renal apical NHE3 activity. The PKC pathway is thought to play a more significant role in modulating NHE3 activity in certain pathophysiologic conditions (e.g., hypoxia, ischemia) in which local production of adenosine is high [for review, see (8)]. By inhibiting NHE3 in particular under these conditions, adenosine could help to improve the oxygen demand and so reinstate the balance of energy supply: demand especially in the S3 segment of the proximal tubule, which is the primary site of injury in renal ischemia (42,43).…”

Section: Discussionmentioning

confidence: 99%

“…Of the four adenosine receptors that have been cloned, A 1 , A 2A , and A 3 adenosine receptors are known to participate in renal physiology (1)(2)(3)(4)(5)(6)(7). Regarding signal transduction, A 1 and A 3 adenosine receptors are positively linked to the phospholipase C (PLC) effector system and negatively coupled to the cAMP/protein kinase A effector system, whereas A 2A receptors stimulate adenylate cyclase and cAMP formation but may also activate alternative signaling pathways (1,8).…”

mentioning

confidence: 99%

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Bimodal Acute Effects of A1 Adenosine Receptor Activation on Na+/H+ Exchanger 3 in Opossum Kidney Cells

Sole¹,

Cerull²,

Petzke³

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Regulation of renal apical Na ϩ /H ϩ exchanger 3 (NHE3) activity by adenosine has been suggested to contribute to acute control of mammalian Na ϩ homeostasis. The mechanism by which adenosine controls NHE3 activity in a renal cell line was examined. The adenosine analog, N 6 -cyclopentyladenosine (CPA) exerts a bimodal effect on NHE3: CPA concentrations Ͼ10 Ϫ8 M inactivate NHE3, whereas concentrations Ͻ10 Ϫ8 M stimulate NHE3 activity. Acute CPA-induced control of NHE3 was blocked by antagonists of A 1 adenosine receptors and inhibition of phospholipase C, pretreatment with BAPTA-AM (chelator of cellular calcium), and exposure to pertussis toxin. Stimulatory and to some extent also inhibitory CPA concentrations attenuated 8-bromo-cAMP and dopaminemediated inhibition of NHE3. BAPTA eliminated the ability of a stimulatory dose of CPA to attenuate 8-bromo-cAMP-induced suppression of NHE3 activity. Upon inhibition of protein kinase C, CPA at an inhibitory dose provoked activation of NHE3, which is partially reverted by 8-bromo-cAMP and suppressed by pre-incubation with BAPTA-AM. Cytochalasin B, an actin-modifying agent, selectively prevented downregulation but did not affect upregulation of NHE3 activity by CPA. In conclusion, these observations demonstrate that (1) CPA modulates NHE3 activity by elevation of cellular Ca 2ϩ exerting a negative control on adenylate cyclase activity, (2) protein kinase C is the determining factor leading to CPAinduced downregulation of NHE3 activity, and (3) alterations of surface NHE3 abundance may contribute to A 1 adenosine receptor-dependent inhibition of NHE3 activity.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Bimodal Acute Effects of A1 Adenosine Receptor Activation on Na+/H+ Exchanger 3 in Opossum Kidney Cells

Sole¹,

Cerull²,

Petzke³

et al. 2003

Journal of the American Society of Nephrology

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“…Adenosine, a ubiquitous purine nucleoside released into the extracellular environment from metabolically active or stressed cells, acts as paracrine regulator of many cellular functions, including those of cell proliferation and differentiation [2][3][4][5]. The regulatory role of extracellular adenosine is based on the activation of cell surface receptors, denoted as A 1 , A 2a , A 2b , and A 3 .…”

Section: Introductionmentioning

confidence: 99%

The pharmacological activation of adenosine A1 and A3 receptors does not modulate the long- or short-term repopulating ability of hematopoietic stem and multipotent progenitor cells in mice

Höfer

Pospı́šil

Hoferová

et al. 2012

Purinergic Signalling

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“…Over the past decade, we have disclosed numerous classes of selective A 1 AR antagonists 31À34 and selective A 3 AR antagonists. 34À37 With the aim to identify novel potent AR antagonists, the class of 3-aryl- [1,2,4]triazino [4,3-a]benzimidazol-4(10H)ones 31,32 was further investigated. A small library of derivatives was synthesized and tested, permitting identification of compound FTBI, featuring a 2-phenylethyl group at the 10-position and a 2-furyl moiety at the 3-position of the triazinobenzimidazole nucleus, with a significant A 2A AR affinity (see Scheme 1).…”

Section: à11mentioning

confidence: 99%

3-(Fur-2-yl)-10-(2-phenylethyl)-[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-one, a Novel Adenosine Receptor Antagonist with A_2A-Mediated Neuroprotective Effects

Scatena

Fornai

Trincavelli

et al. 2011

ACS Chem. Neurosci.

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In this study, compound FTBI (3-(2-furyl)-10-(2-phenylethyl) [1,2,4]triazino [4,3-a]benzimidazol-4(10H)one) was selected from a small library of triazinobenzimidazole derivatives as a potent A 2A adenosine receptor (AR) antagonist and tested for its neuroprotective effects against two different kinds of dopaminergic neurotoxins, 1-methyl-4-phenylpyridinium (MPP+) and methamphetamine (METH), in rat PC12 and in human neuroblastoma SH-SY5Y cell lines. FTBI, in a concentration range corresponding to its affinity for A 2A AR subtype, significantly increased the number of viable PC12 cells after their exposure to METH and, to a similar extent, to MPP+, as demonstrated in both trypan blue exclusion assay and in cytological staining. These neuroprotective effects were also observed with a classical A 2A AR antagonist, ZM241385, and appeared to be completely counteracted by the AR agonist, NECA, supporting A 2A ARs are directly involved in FTBI-mediated effects. Similarly, in human SH-SY5Y cells, FTBI was able to prevent cell toxicity induced by MPP+ and METH, showing that this A 2A AR antagonist has a neuroprotective effect independently by the specific cell model. Altogether these results demonstrate that the A 2A AR blockade mediates cell protection against neurotoxicity induced by dopaminergic neurotoxins in dopamine containing cells, supporting the potential use of A 2A AR antagonists in dopaminergic degenerative diseases including Parkinson's disease.

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Adenosine receptors: new opportunities for future drugs

Cited by 278 publications

References 131 publications

Bimodal Acute Effects of A1 Adenosine Receptor Activation on Na+/H+ Exchanger 3 in Opossum Kidney Cells

Bimodal Acute Effects of A1 Adenosine Receptor Activation on Na+/H+ Exchanger 3 in Opossum Kidney Cells

The pharmacological activation of adenosine A1 and A3 receptors does not modulate the long- or short-term repopulating ability of hematopoietic stem and multipotent progenitor cells in mice

3-(Fur-2-yl)-10-(2-phenylethyl)-[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-one, a Novel Adenosine Receptor Antagonist with A_2A-Mediated Neuroprotective Effects

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Adenosine receptors: new opportunities for future drugs

Cited by 278 publications

References 131 publications

Bimodal Acute Effects of A1 Adenosine Receptor Activation on Na+/H+ Exchanger 3 in Opossum Kidney Cells

Bimodal Acute Effects of A1 Adenosine Receptor Activation on Na+/H+ Exchanger 3 in Opossum Kidney Cells

The pharmacological activation of adenosine A1 and A3 receptors does not modulate the long- or short-term repopulating ability of hematopoietic stem and multipotent progenitor cells in mice

3-(Fur-2-yl)-10-(2-phenylethyl)-[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-one, a Novel Adenosine Receptor Antagonist with A2A-Mediated Neuroprotective Effects

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3-(Fur-2-yl)-10-(2-phenylethyl)-[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-one, a Novel Adenosine Receptor Antagonist with A_2A-Mediated Neuroprotective Effects