CGS 21680: A Potent Selective Adenosine A<sub>2</sub> Receptor Agonist

Webb, Randy L.; Sills, Matthew A.; Chovan, James P.; Balwierczak, Joseph L.; Francis, J. E.

doi:10.1111/j.1527-3466.1992.tb00235.x

Cited by 18 publications

(8 citation statements)

References 111 publications

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“…Functionally, treated lungs showed improved mean airway pressure and expiratory minute volume. Interestingly, we found that the most optimal recorded gases occurred during the first and second hours of EVLP, an observation that may be secondary to the compound’s short half-life (25 to 30 minutes) (24). …”

Section: Discussionmentioning

confidence: 95%

Adenosine A2A Agonist Improves Lung Function During Ex Vivo Lung Perfusion

Emaminia

LaPar

Zhao

et al. 2011

The Annals of Thoracic Surgery

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Background Ex-vivo lung perfusion (EVLP) is a novel technique to assess, and potentially repair marginal lungs that may otherwise be rejected for transplantation. Adenosine has been shown to protect against lung ischemia-reperfusion injury through its A2A receptor. We hypothesized that combining EVLP with adenosine A2A receptor agonist treatment would enhance lung functional quality and increase donor lung usage. Methods Eight bilateral pig lungs were harvested and flushed with cold Perfadex. After 14 hours storage at 4°C, EVLP was performed for 5 hours on two explanted lung groups: 1) Control group lungs (n=4), were perfused with Steen Solution and Dimethyl sulfoxide (DMSO), and 2) treated group lungs (n=4) received 10μM CGS21680, a selective A2A receptor agonist, in a Steen Solution-primed circuit. Lung histology, tissue cytokines, gas analysis and pulmonary function were compared between groups. Results Treated lungs demonstrated significantly less edema as reflected by wet-dry weight ratio (6.6 vs. 5.2, p<0.03) and confirmed by histology. In addition, treated lung demonstrated significantly lower levels of interferon gamma (45.1 vs. 88.5, p<0.05). Other measured tissue cytokines (interleukin (IL) 1 beta, IL-6, and IL-8) were lower in treatment group, but values failed to reach statistical significance. Oxygenation index was improved in the treated group (1.5 vs. 2.3, p<0.01) as well as mean airway pressure (10.3 vs. 13 p<0.009). Conclusions EVLP is a novel and efficient way to assess and optimize lung function and oxygen exchange within donor lungs, and the use of adenosine A2A agonist potentiates its potential. EVLP with the concomitant administration of A2A agonist may enhance donor lung quality and could increase the donor lung pool for transplantation.

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Section: Discussionmentioning

confidence: 95%

Adenosine A2A Agonist Improves Lung Function During Ex Vivo Lung Perfusion

Emaminia

LaPar

Zhao

et al. 2011

The Annals of Thoracic Surgery

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“…A rapid restoration of normal blood perfusion may be expected to lead to a better outcome from an ischaemic insult. It should be noted that the tolerance to the hypotensive effects of selective A 2A receptor agonists has been reported after continuous infusion 47 , but not after chronic injections 48 .…”

Section: Acute Versus Chronic Administration On Neuroprotection From mentioning

confidence: 97%

Adenosine receptor ligands: differences with acute versus chronic treatment

Jacobson

Lubitz

Daly

et al. 1996

Trends in Pharmacological Sciences

244

180

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Adenosine receptors have been the target of intense research with respect to potential use of selective ligands in a variety of therapeutic areas. Caffeine and theophylline are adenosine receptor antagonists, and over the past three decades a wide range of selective agonists and antagonists for adenosine receptor subtypes have been developed. A complication to the therapeutic use of adenosine receptor ligands is the observation that the effects of acute administration of a particular ligand can be diametrically opposite to the chronic effects of the same ligand. This 'effect inversion' is discussed here by Ken Jacobson and colleagues, and has been observed for effects on cognitive processes, seizures and ischaemic damage.

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“…Based on these reports and on other findings, it was suggested that [3H]-NECA also labels the adenotin binding site . Trying to overcome these discrepancies we had studied (Varani et al, 1994) the human platelet adenosine receptor using the A2a-selective radioligand [3H]-CGS 21680 which has been reported to interact with the high affinity A2a adenosine receptor in both binding and adenylyl cyclase assays (Jarvis et al, 1989;Webb et al, 1992;Mathot et al, 1995). Like NECA, CGS 21680 proved to be unsatisfactory for the characterization of A2a human platelet receptors, since it also seemed to label the adenotin binding site (Varani et al, 1994).…”

Section: Discussionmentioning

confidence: 99%