Abstract
The pharmacological activity of diadenosine polyphosphates was investigated at three recombinant P2X receptors (rat P2X1, rat P2X3, rat P2X4) expressed in Xenopus oocytes and studied under voltage-clamp conditions. For the rat P2X1 receptor, only P1,P6-diadenosine hexaphosphate (Ap6A) was a full agonist yet 2-3 folds less potent than ATP. At rat P2X3, P1,p4-diadenosine tetraphosphate (Ap4A), P1,P5-diadenosine pentaphosphate (Ap5A) and Ap6A were full agonists and more potent than ATP. Ap4A alone was equipotent with ATP at rat P2X4, but only as a partial agonist. Compared to known data for rat P2X2 and human P2X1 receptors, our findings contrast with rat P2X2 where only Ap4A is a full agonist although four folds less potent than ATP. At rat and human orthologues of P2X1, Ap5A was a partial agonist with similar potency. These data provide a useful basis for selective agonists of P2X receptor subunits.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenine Nucleotides
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Adenosine Triphosphate / pharmacology
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Animals
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Binding, Competitive / drug effects
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Dinucleoside Phosphates / metabolism
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Dinucleoside Phosphates / pharmacology*
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Dose-Response Relationship, Drug
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Membrane Potentials / drug effects
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Oocytes / drug effects
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Oocytes / physiology
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Purinergic P2 Receptor Agonists
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RNA, Messenger / administration & dosage
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RNA, Messenger / genetics
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Rats
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Receptors, Purinergic P2 / genetics
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Receptors, Purinergic P2 / metabolism*
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Receptors, Purinergic P2X
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Receptors, Purinergic P2X3
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Receptors, Purinergic P2X4
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Xenopus
Substances
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Adenine Nucleotides
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Dinucleoside Phosphates
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P2RX3 protein, human
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P2RX4 protein, human
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P2rx3 protein, rat
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P2rx4 protein, rat
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Purinergic P2 Receptor Agonists
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RNA, Messenger
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Receptors, Purinergic P2
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Receptors, Purinergic P2X
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Receptors, Purinergic P2X3
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Receptors, Purinergic P2X4
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P(1),P(5)-di(adenosine-5'-)pentaphosphate
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diadenosine tetraphosphate
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diadenosine triphosphate
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diadenosine 5',5''''-P1,P6-hexaphosphate
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Adenosine Triphosphate