ArticleProceedings of the National Academy of Sciences of the United States of America2014
Uridine adenosine tetraphosphate is a novel neurogenic P2Y1 receptor activator in the gut.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Purinergic P2YPurinergic signalling · 2025Article
- Exploring bias in platelet P2YBritish journal of pharmacology · 2024Review
- Stimulation of platelet P2YBritish journal of pharmacology · 2024Article
- Transcriptome analysis of mesenchymal stromal cells of the large and small intestinal smooth muscle layers reveals a unique gastrontestinal stromal signature.Biochemistry and biophysics reports · 2023Article
- Urinary ATP Levels Are Controlled by Nucleotidases Released from the Urothelium in a Regulated Manner.Metabolites · 2022Article
- CaAdvances in experimental medicine and biology · 2022Article
- Neurotransmitters responsible for purinergic motor neurotransmission and regulation of GI motility.Autonomic neuroscience : basic & clinical · 2021Article
- Nucleotide P2YPurinergic signalling · 2020Article
- Extracellular metabolism of the enteric inhibitory neurotransmitter β-nicotinamide adenine dinucleotide (β-NAD) in the murine colon.The Journal of physiology · 2020Article
- NTPDase1 and -2 are expressed by distinct cellular compartments in the mouse colon and differentially impact colonic physiology and function after DSS colitis.American journal of physiology. Gastrointestinal and liver physiology · 2019Article
- Comparison of inhibitory neuromuscular transmission in the Cynomolgus monkey IAS and rectum: special emphasis on differences in purinergic transmission.The Journal of physiology · 2018Article
- Divergent coronary flow responses to uridine adenosine tetraphosphate in atherosclerotic ApoE knockout mice.Purinergic signalling · 2017Article
- Purinergic drug targets for gastrointestinal disorders.Current opinion in pharmacology · 2017Review
- Loss of nitric oxide-mediated inhibition of purine neurotransmitter release in the colon in the absence of interstitial cells of Cajal.American journal of physiology. Gastrointestinal and liver physiology · 2017Article
- Impaired Aortic Contractility to Uridine Adenosine Tetraphosphate in Angiotensin II-Induced Hypertensive Mice: Receptor Desensitization?American journal of hypertension · 2017Article
- R-Type CaExperimental physiology · 2017Article
- A commonly used ecto-ATPase inhibitor, ARL-67156, blocks degradation of ADP more than the degradation of ATP in murine colon.Neurogastroenterology and motility · 2016Article
- Medicinal chemistry of adenosine, P2Y and P2X receptors.Neuropharmacology · 2016Review
- Appropriate experimental approach is critical for identifying neurotransmitter substances: application to enteric purinergic neurotransmission.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- Mechanisms underlying uridine adenosine tetraphosphate-induced vascular contraction in mouse aorta: Role of thromboxane and purinergic receptors.Vascular pharmacology · 2015Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Enteric purinergic motor neurotransmission, acting through P2Y1 receptors (P2Y1R), mediates inhibitory neural control of the intestines. Recent studies have shown that NAD(+) and ADP ribose better meet criteria for enteric inhibitory neurotransmitters in colon than ATP or ADP. Here we report that human and murine colon muscles also release uridine adenosine tetraphosphate (Up4A) spontaneously and upon stimulation of enteric neurons. Release of Up4A was reduced by tetrodotoxin, suggesting that at least a portion of Up4A is of neural origin. Up4A caused relaxation (human and murine colons) and hyperpolarization (murine colon) that was blocked by the P2Y1R antagonist, MRS 2500, and by apamin, an inhibitor of Ca(2+)-activated small-conductance K(+) (SK) channels. Up4A responses were greatly reduced or absent in colons of P2ry1(-/-) mice. Up4A induced P2Y1R-SK-channel-mediated hyperpolarization in isolated PDGFRα(+) cells, which are postjunctional targets for purinergic neurotransmission. Up4A caused MRS 2500-sensitive Ca(2+) transients in human 1321N1 astrocytoma cells expressing human P2Y1R. Up4A was more potent than ATP, ADP, NAD(+), or ADP ribose in colonic muscles. In murine distal colon Up4A elicited transient P2Y1R-mediated relaxation followed by a suramin-sensitive contraction. HPLC analysis of Up4A degradation suggests that exogenous Up4A first forms UMP and ATP in the human colon and UDP and ADP in the murine colon. Adenosine then is generated by extracellular catabolism of ATP and ADP. However, the relaxation and hyperpolarization responses to Up4A are not mediated by its metabolites. This study shows that Up4A is a potent native agonist for P2Y1R and SK-channel activation in human and mouse colon.
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