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 P2X(1), P2X(3), and heteromeric P2X(2/3) receptors. The rank order of potency for TNP-ATP-sensitive excitation was determined as follows (30 muM 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. NeuroReport 12:679-682 (C) 2001 Lippincott Williams & Wilkins.