Diadenosine pentaphosphate is more potent than ATP at P2X receptors in isolated rat vagus nerve.
The effects of diadenosine pentaphosphate (Ap5A), diadenosine tetraphosphate (Ap4A), alpha,beta-methyleneATP (alpha,beta-meATP), and ATP were studied on the excitability of unmyelinated axons in isolated rat vagus nerve by means of a computerized threshold tracking technique. All purinergic compounds produced an increase in excitability, however, only the effects of alpha,beta-meATP and of Ap5A were strongly reduced by 2'- (or 3') -O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP), a selective blocker for P2X1, P2X3, and heteromeric P2X2/3 receptors. The rank order of potency for TNP-ATP-sensitive excitation was determined as follows (30 microM each): alpha,beta-meATP >Ap5A >> Ap4A = ATP. These data suggest that Ap5A might be an important naturally occurring agonist for P2X receptors at the axonal membrane of unmyelinated, including nociceptive, nerve fibres.
Department of Physiology, University of Munich, Germany.
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Burgstahler
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Grafe
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058469:Receptors, Purinergic P2X; D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3; D014630:Vagus Nerve / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D015226:Dinucleoside Phosphates; C546403:P2rx2 protein, rat; C546410:P2rx3 protein, rat; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3; D014662:Vasoconstrictor Agents; C012275:P(1),P(5)-di(adenosine-5'-)pentaphosphate; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate