What is the clinical evidence from this study?

Study design: Other. Intervention: Nucleotides and antagonists (e.g., AR-C67085, suramin). Primary outcome: Pharmacological characterization (potency and efficacy) of the recombinant human P2Y11 receptor.

What question did this study set out to answer?

To characterize the pharmacological properties and agonist-antagonist selectivity of the recombinant human P2Y11 receptor coupled to dual intracellular signaling cascades.

November 1, 1999British Journal of PharmacologyOpen Access

Pharmacological characterization of the human P2Y11 receptor

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Key result

The ATP derivative AR-C67085 was the most potent agonist of the recombinant human P2Y11 receptor, which is coupled to both phosphoinositide and cyclic AMP pathways and competitively antagonized by suramin.

Population

Recombinant human P2Y11 receptor stably expressed in two cell lines: 1321N1 astrocytoma cells and CHO-K1 cells

Design

Preclinical

Authors

DCDidier CommuniUniversité Libre de Bruxelles BRBernard RobayeInstitut Belge pour la Sécurité Routière JBJean‐Marie BoeynaemsUniversité Libre de Bruxelles

Discussion

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Implication

Consistent agonist profiling across P2Y11 pathways; extends recombinant models but leaves clinical cardiovascular translation open.

Key Points

To characterize the pharmacological properties and agonist-antagonist selectivity of the recombinant human P2Y11 receptor coupled to dual intracellular signaling cascades.
Stably expressed recombinant human P2Y11 receptors in 1321N1 astrocytoma cells to measure inositol trisphosphate levels and in CHO-K1 cells to assess cyclic AMP production.
Evaluated the potency orders, partial agonism, and antagonist profiles of multiple synthetic and endogenous nucleotide analogues across both pathways.
The rank order of agonist potency was ATPgammaS ≈ BzATP > dATP > ATP > ADPbetaS > 2MeSATP across both signaling cascades, with the nucleotide derivative AR-C67085 demonstrating the highest overall potency.
ADPbetaS, AMPalphaS, and A3P5PS acted as partial agonists that attenuated full ATP-mediated responses at high concentrations.
Suramin functioned as a competitive antagonist with an apparent Ki of 0.82 ± 0.07 µM, whereas reactive blue 2 was less potent and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid showed no antagonistic activity.

Structured PICO

Population

Recombinant human P2Y11 receptor stably expressed in two cell lines: 1321N1 astrocytoma cells and CHO-K1 cells

Intervention

Various nucleotides (ATPgammaS, BzATP, dATP, ATP, ADPbetaS, 2MeSATP, AMPalphaS, A3P5PS, AR-C67085) and antagonists (suramin, reactive blue 2, pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid)

Outcome

Pharmacological characterization including rank order of potency, agonist/antagonist activity, and receptor coupling to phosphoinositide and cyclic AMP pathwayssurrogate

The pharmacological profile of the recombinant human P2Y11 receptor closely matches the cyclic AMP-coupled P2 receptor in HL-60 cells, identifying AR-C67085 as a potent agonist and suramin as a competitive antagonist.

Cite This Study

Communi et al. (1999) studied this question. Nucleotides and antagonists (e.g., AR-C67085, suramin) was evaluated on Pharmacological characterization (potency and efficacy) of the recombinant human P2Y11 receptor. The ATP derivative AR-C67085 was the most potent agonist of the recombinant human P2Y11 receptor, which is coupled to both phosphoinositide and cyclic AMP pathways and competitively antagonized by suramin.

synapsesocial.com/papers/6a6bd4f3547974b2dbf4699f https://doi.org/10.1038/sj.bjp.0702909

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Pharmacological characterization of the human P2Y11 receptor

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Pharmacological characterization of the human P2Y11 receptor

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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Also Consider