Source 1review2000British Journal of Pharmacology
Toolkit/[3H]-CGS 21680
[3H]-CGS 21680
Taxonomy: Technique Branch / Method. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
The A2A selective agonist [3H]-CGS 21680... has also been used by Varani et al. (1994) in human platelet membranes... although CGS 21680 interacts with the platelet A2A adenosine receptor, like NECA, it proved to be unsatisfactory for the characterization of A2A human platelet receptors... in the purified protein preparation [3H]-CGS 21680 interacts with one recognition site only, with an affinity in the nanomolar range.
Usefulness & Problems
Why this is useful
This tritiated agonist is used to probe A2A receptor binding. The review says it can interact with the platelet A2A receptor but performs poorly in crude platelet membranes and better in purified receptor preparations.; A2A receptor binding studies in purified platelet receptor preparations; functional interrogation of A2A receptor pharmacology as an agonist ligand
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This tritiated agonist is used to probe A2A receptor binding. The review says it can interact with the platelet A2A receptor but performs poorly in crude platelet membranes and better in purified receptor preparations.
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A2A receptor binding studies in purified platelet receptor preparations
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functional interrogation of A2A receptor pharmacology as an agonist ligand
Problem solved
It offered a selective agonist-based route to study A2A receptors when better tools were still being developed. In purified preparations it gave more receptor-like binding behavior.; provided an A2A-selective agonist radioligand option for receptor studies
Source:
It offered a selective agonist-based route to study A2A receptors when better tools were still being developed. In purified preparations it gave more receptor-like binding behavior.
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provided an A2A-selective agonist radioligand option for receptor studies
Problem links
provided an A2A-selective agonist radioligand option for receptor studies
LiteratureIt offered a selective agonist-based route to study A2A receptors when better tools were still being developed. In purified preparations it gave more receptor-like binding behavior.
Source:
It offered a selective agonist-based route to study A2A receptors when better tools were still being developed. In purified preparations it gave more receptor-like binding behavior.
Taxonomy & Function
Primary hierarchy
Technique Branch
Method: A concrete measurement method used to characterize an engineered system.
Techniques
Functional AssayTarget processes
No target processes tagged yet.
Implementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationoperating role: sensor
Use requires the radioligand and receptor-containing membrane or purified protein preparations. The review specifically describes CHAPS extraction and PEG precipitation as preparation steps that improved interpretability.; works better after receptor purification or partial purification steps that reduce adenotin interference; requires radioligand binding assay capability and appropriate receptor preparation
It does not reliably solve non-receptor binding problems in platelet membranes. The review also notes that agonist radioligands are not ideal because binding depends on G protein state.; unsatisfactory for characterization of A2A receptors in human platelet membranes; suggested to label low-affinity non-receptor sites in membrane preparations; agonist radioligand behavior is influenced by G protein state
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
Activation of platelet A2A receptors increases cyclic AMP accumulation and decreases platelet aggregation.
Adenotin is a low-affinity non-receptor binding protein that confounds membrane binding analyses of A2A receptors and precluded direct characterization in platelet membranes with earlier ligands.
A2A adenosine receptors are expressed in human peripheral blood cells including platelets, lymphocytes, and neutrophils and are linked to platelet antiaggregatory, neutrophil antiinflammatory, and immune-modulatory effects.
[3H]-CGS 21680 interacts with platelet A2A receptors but is unsatisfactory in human platelet membranes because it also labels low-affinity non-receptor sites; it becomes more adequate after purification that reduces adenotin interference.
[3H]-NECA is unsatisfactory for direct characterization of human platelet A2A receptors because much of its binding in platelet membranes is to non-receptor sites.
[3H]-XAC does not permit satisfactory A2A receptor binding studies because of high non-specific binding.
[3H]-SCH 58261 enabled satisfactory binding characterization of the A2A receptor subtype in human platelets and is presented as the first radioligand to do so.
Approval Evidence
1 source1 linked approval claimfirst-pass slug 3h-cgs-21680
The A2A selective agonist [3H]-CGS 21680... has also been used by Varani et al. (1994) in human platelet membranes... although CGS 21680 interacts with the platelet A2A adenosine receptor, like NECA, it proved to be unsatisfactory for the characterization of A2A human platelet receptors... in the purified protein preparation [3H]-CGS 21680 interacts with one recognition site only, with an affinity in the nanomolar range.
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tool limitationsupports
[3H]-CGS 21680 interacts with platelet A2A receptors but is unsatisfactory in human platelet membranes because it also labels low-affinity non-receptor sites; it becomes more adequate after purification that reduces adenotin interference.
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Comparisons
Source-stated alternatives
The review contrasts it with [3H]-NECA, [3H]-XAC, and especially [3H]-SCH 58261. [3H]-SCH 58261 is presented as the more satisfactory antagonist radioligand for direct A2A characterization.
Source:
The review contrasts it with [3H]-NECA, [3H]-XAC, and especially [3H]-SCH 58261. [3H]-SCH 58261 is presented as the more satisfactory antagonist radioligand for direct A2A characterization.
Source-backed strengths
reported to interact with high affinity A2A receptors in binding and adenylyl cyclase assays; appears adequate in purified platelet receptor preparations according to the review
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reported to interact with high affinity A2A receptors in binding and adenylyl cyclase assays
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appears adequate in purified platelet receptor preparations according to the review
Compared with [3H]-NECA
The review contrasts it with [3H]-NECA, [3H]-XAC, and especially [3H]-SCH 58261. [3H]-SCH 58261 is presented as the more satisfactory antagonist radioligand for direct A2A characterization.
Shared frame: source-stated alternative in extracted literature
Strengths here: reported to interact with high affinity A2A receptors in binding and adenylyl cyclase assays; appears adequate in purified platelet receptor preparations according to the review.
Relative tradeoffs: unsatisfactory for characterization of A2A receptors in human platelet membranes; suggested to label low-affinity non-receptor sites in membrane preparations; agonist radioligand behavior is influenced by G protein state.
Source:
The review contrasts it with [3H]-NECA, [3H]-XAC, and especially [3H]-SCH 58261. [3H]-SCH 58261 is presented as the more satisfactory antagonist radioligand for direct A2A characterization.
Compared with [3H]-SCH 58261
The review contrasts it with [3H]-NECA, [3H]-XAC, and especially [3H]-SCH 58261. [3H]-SCH 58261 is presented as the more satisfactory antagonist radioligand for direct A2A characterization.
Shared frame: source-stated alternative in extracted literature
Strengths here: reported to interact with high affinity A2A receptors in binding and adenylyl cyclase assays; appears adequate in purified platelet receptor preparations according to the review.
Relative tradeoffs: unsatisfactory for characterization of A2A receptors in human platelet membranes; suggested to label low-affinity non-receptor sites in membrane preparations; agonist radioligand behavior is influenced by G protein state.
Source:
The review contrasts it with [3H]-NECA, [3H]-XAC, and especially [3H]-SCH 58261. [3H]-SCH 58261 is presented as the more satisfactory antagonist radioligand for direct A2A characterization.
Compared with [3H]-XAC
The review contrasts it with [3H]-NECA, [3H]-XAC, and especially [3H]-SCH 58261. [3H]-SCH 58261 is presented as the more satisfactory antagonist radioligand for direct A2A characterization.
Shared frame: source-stated alternative in extracted literature
Strengths here: reported to interact with high affinity A2A receptors in binding and adenylyl cyclase assays; appears adequate in purified platelet receptor preparations according to the review.
Relative tradeoffs: unsatisfactory for characterization of A2A receptors in human platelet membranes; suggested to label low-affinity non-receptor sites in membrane preparations; agonist radioligand behavior is influenced by G protein state.
Source:
The review contrasts it with [3H]-NECA, [3H]-XAC, and especially [3H]-SCH 58261. [3H]-SCH 58261 is presented as the more satisfactory antagonist radioligand for direct A2A characterization.
Ranked Citations
- 1.