ArticleMolecular pharmacology2001
Allosteric modulation of A(3) adenosine receptors by a series of 3-(2-pyridinyl)isoquinoline derivatives.
Article in Molecular pharmacology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
35 citing papers in PubMed, 78 citations in OpenAlex.
- From empirical screening to lipid trolling: the evolution of extrahelical allosteric modulators of AMedicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Species dependence of APurinergic signalling · 2023Review
- Structure-Activity Studies of 1Journal of medicinal chemistry · 2022Article
- International Union of Basic and Clinical Pharmacology. CXII: Adenosine Receptors: A Further Update.Pharmacological reviews · 2022Review
- Allosteric Modulation of Adenosine AInternational journal of molecular sciences · 2022Review
- Update on the recent development of allosteric modulators for adenosine receptors and their therapeutic applications.Frontiers in pharmacology · 2022Review
- Binding kinetics of ligands acting at GPCRs.Molecular and cellular endocrinology · 2019Review
- AMedicinal research reviews · 2018Review
- Synthesis of novel (benzimidazolyl)isoquinolinols and evaluation as adenosine A1 receptor tools.RSC advances · 2018Article
- Species differences and mechanism of action of APurinergic signalling · 2018Article
- Prediction of consensus binding mode geometries for related chemical series of positive allosteric modulators of adenosine and muscarinic acetylcholine receptors.Journal of computational chemistry · 2017Article
- Molecular mechanism of allosteric modulation at GPCRs: insight from a binding kinetics study at the human A1 adenosine receptor.British journal of pharmacology · 2014Article
- Kinetic analysis of antagonist-occupied adenosine-A3 receptors within membrane microdomains of individual cells provides evidence of receptor dimerization and allosterism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
- Allosteric interactions at adenosine A(1) and A(3) receptors: new insights into the role of small molecules and receptor dimerization.British journal of pharmacology · 2014Review
- Protection from myocardial ischemia/reperfusion injury by a positive allosteric modulator of the A₃ adenosine receptor.The Journal of pharmacology and experimental therapeutics · 2012Article
- International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and classification of adenosine receptors--an update.Pharmacological reviews · 2011Review
- Allosteric modulation of purine and pyrimidine receptors.Advances in pharmacology (San Diego, Calif.) · 2011Review
- The effect of allosteric modulators on the kinetics of agonist-G protein-coupled receptor interactions in single living cells.Molecular pharmacology · 2010Article
- Antagonist selective modulation of adenosine A1 and A3 receptor pharmacology by the food dye Brilliant Black BN: evidence for allosteric interactions.Molecular pharmacology · 2010Article
- Adenosine and the auditory system.Current neuropharmacology · 2009Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Allosteric modulators of A(1) and A(2A) adenosine receptors have been described; however, for the A(3) adenosine receptor, neither an allosteric site nor a compound with allosteric effects has been described. In this study, the allosteric modulation of human A(3) adenosine receptors by a series of 3-(2-pyridinyl)isoquinoline derivatives was investigated by examining their effects on the dissociation of the agonist radioligand, [(125)I]N(6)-(4-amino-3-iodobenzyl)-5'-N-methylcarboxamidoadenosine (I-AB-MECA), from the receptor. Several 3-(2-pyridinyl)isoquinoline derivatives, including VUF5455, VUF8502, VUF8504, and VUF8507, slowed the dissociation of the agonist radioligand [(125)I]I-AB-MECA in a concentration-dependent manner, suggesting an allosteric interaction. These compounds had no effect on the dissociation of the radiolabeled antagonist [(3)H]PSB-11 from the A(3) adenosine receptor, suggesting a selective enhancement of agonist binding. By comparison, compounds of similar structure (VUF8501, VUF8503, VUF8505), the classical adenosine receptor antagonist CGS15943 and the A(1) receptor allosteric enhancer PD81723 did not significantly influence the dissociation rate of [(125)I]I-AB-MECA. The effect of agonist on forskolin-induced cAMP production was significantly enhanced by VUF5455. When the subtype-selectivity of the allosteric enhancement was tested the compounds had no effect on the dissociation of either [(3)H]N(6)-[(R)-phenylisopropyl]adenosine from the A(1) adenosine receptor or [(3)H]CGS21680 from the A(2A) adenosine receptor. Probing of structure-activity relationships suggested that a carbonyl group is essential for allosterism but preferred only for competitive antagonism. The presence of a 7-methyl group decreased the competitive binding affinity without a major loss of the allosteric enhancing activity, suggesting that the structural requirements for allosteric enhancement might be distinct from those for competitive antagonism.
Indexed as
Identifiers
11641434PMC3953614W2166225079What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.