Abstract
Ribose-based nucleoside 5'-diphosphates and triphosphates and related nucleotides were compared in their potency at the P2Y receptors with the corresponding nucleoside 5'-phosphonate derivatives. Phosphonate derivatives of UTP and ATP activated the P2Y(2) receptor but were inactive or weakly active at P2Y(4) receptor. Uridine 5'-(diphospho)phosphonate was approximately as potent at the P2Y(2) receptor as at the UDP-activated P2Y(6) receptor. These results suggest that removal of the 5'-oxygen atom from nucleotide agonist derivatives reduces but does not prevent interaction with the P2Y(2) receptor. Uridine 5'-(phospho)phosphonate as well as the 5'-methylenephosphonate equivalent of UMP were inactive at the P2Y(4) receptor and exhibited maximal effects at the P2Y(2) receptor that were 50% of that of UTP suggesting novel action of these analogues.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
MeSH terms
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Adenosine Diphosphate / analogs & derivatives
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Adenosine Diphosphate / chemical synthesis
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Adenosine Diphosphate / chemistry
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Adenosine Triphosphate / analogs & derivatives
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Adenosine Triphosphate / chemical synthesis
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Adenosine Triphosphate / chemistry
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Cell Line, Tumor
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Humans
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Nucleotides / chemical synthesis*
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Nucleotides / chemistry
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Purinergic P2 Receptor Agonists*
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Receptors, Purinergic P2 / metabolism
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Recombinant Proteins / agonists
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Recombinant Proteins / metabolism
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Uridine Diphosphate / analogs & derivatives
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Uridine Diphosphate / chemical synthesis
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Uridine Diphosphate / chemistry
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Uridine Triphosphate / analogs & derivatives
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Uridine Triphosphate / chemical synthesis
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Uridine Triphosphate / chemistry
Substances
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Nucleotides
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Purinergic P2 Receptor Agonists
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Receptors, Purinergic P2
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Recombinant Proteins
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Uridine Diphosphate
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Adenosine Diphosphate
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Adenosine Triphosphate
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Uridine Triphosphate