ArticleThe Journal of pharmacology and experimental therapeutics2004
Induction of novel agonist selectivity for the ADP-activated P2Y1 receptor versus the ADP-activated P2Y12 and P2Y13 receptors by conformational constraint of an ADP analog.
Article in The Journal of pharmacology and experimental therapeutics, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- Characterization of Potency of the P2Y13 Receptor Agonists: A Meta-Analysis.International journal of molecular sciences · 2021Pooled it
- Advances in nucleotide-based P2Y₁ antagonism: implications for cardiovascular therapeutics.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Pharmacological characterization of P2Y receptor subtypes - an update.Purinergic signalling · 2024Review
- GRK2 regulates ADP signaling in platelets via P2Y1 and P2Y12.Blood advances · 2022Article
- Oscillatory calcium release and sustained store-operated oscillatory calcium signaling prevents differentiation of human oligodendrocyte progenitor cells.Scientific reports · 2022Article
- P2 Receptors in Cardiac Myocyte Pathophysiology and Mechanotransduction.International journal of molecular sciences · 2020Review
- Update of P2Y receptor pharmacology: IUPHAR Review 27.British journal of pharmacology · 2020Review
- A novel postsynaptic signal pathway of sympathetic neural regulation of murine colonic motility.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Survey of ribose ring pucker of signaling nucleosides and nucleotides.Nucleosides, nucleotides & nucleic acids · 2020Article
- Purinergic Signaling in Controlling Macrophage and T Cell Functions During Atherosclerosis Development.Frontiers in immunology · 2020Review
- Eosinophils and Purinergic Signaling in Health and Disease.Frontiers in immunology · 2020Review
- P2Y1 receptor blockade normalizes network dysfunction and cognition in an Alzheimer's disease model.The Journal of experimental medicine · 2018Article
- Medicinal chemistry of adenosine, P2Y and P2X receptors.Neuropharmacology · 2016Review
- On the selectivity of the Gαq inhibitor UBO-QIC: A comparison with the Gαi inhibitor pertussis toxin.Biochemical pharmacology · 2016Article
- Modeling ligand recognition at the P2Y12 receptor in light of X-ray structural information.Journal of computer-aided molecular design · 2015Article
- β-Nicotinamide adenine dinucleotide acts at prejunctional adenosine A1 receptors to suppress inhibitory musculomotor neurotransmission in guinea pig colon and human jejunum.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- RASA3 is a critical inhibitor of RAP1-dependent platelet activation.The Journal of clinical investigation · 2015Article
- Impaired cognition after stimulation of P2Y1 receptors in the rat medial prefrontal cortex.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015Article
- Platelet-derived growth factor receptor-α-positive cells and not smooth muscle cells mediate purinergic hyperpolarization in murine colonic muscles.American journal of physiology. Cell physiology · 2014Article
- P2Y1 receptor-mediated potentiation of inspiratory motor output in neonatal rat in vitro.The Journal of physiology · 2014Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
ADP is the cognate agonist of the P2Y1, P2Y12, and P2Y13 receptors. With the goal of identifying a high potency agonist that selectively activates the P2Y1 receptor, we examined the pharmacological selectivity of the conformationally constrained non-nucleotide analog (N)-methanocarba-2MeSADP [(1'S,2'R, 3'S,4'R,5'S)-4-[(6-amino-2-methylthio-9H-purin-9-yl)-1-diphosphoryloxymethyl]bicyclo[3.1.0]hexane-2,3-diol] among the three ADP-activated receptors. Each P2Y receptor was expressed transiently in COS-7 cells, and inositol lipid hydrolysis was quantified as a measure of receptor activity. In the case of the Gi-linked P2Y12 and P2Y13 receptors, a chimeric G protein, Galphaq/i, was coexpressed to confer a capacity of these Gi-linked receptors to activate phospholipase C. 2MeSADP (2-methylthio-ADP) was a potent agonist at all three receptors exhibiting EC50 values in the sub to low nanomolar range. In contrast, whereas (N)-methanocarba-2MeSADP was an extremely potent (EC50=1.2 +/- 0.2 nM) agonist at the P2Y1 receptor, this non-nucleotide analog exhibited no agonist activity at the P2Y12 receptor and very low activity at the P2Y13 receptor. (N)-Methanocarba-2MeSADP also failed to block the action of 2MeSADP at the P2Y12 and P2Y13 receptors, indicating that the (N)-methanocarba analog is not an antagonist at these receptors. The P2Y1 receptor selectivity of (N)-methanocarba-2MeSADP was confirmed in human platelets where it induced the shape change promoted by P2Y1 receptor activation without inducing the sustained platelet aggregation that requires simultaneous activation of the P2Y12 receptor. These results provide the first demonstration of a high-affinity agonist that discriminates among the three ADP-activated P2Y receptors, and therefore, introduce a potentially important new pharmacological tool for delineation of the relative biological action of these three signaling proteins.
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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.