Ionotropic ATP

Ionotropic ATP receptors ATP is an excitatory NT in the central nervous system (CNS) and the peripheral nervous system (PNS). ATP acts via ionotropic, oligomeric P2X receptors that form ATP-gated Na+ and K+ channels which also have a significant permeability for Ca2+. ATP also acts via excitatory, metabotropic, G protein-linked P2Y receptors (see Chapter 5). 

In behavioral tests, the actions of peripherally-administered ATP are pro-nociceptive. These nociceptive responses have been suggested to be due to direct activation of peripheral nerve terminals (Hies and Norenberg, 1993). ATP produces depolarization when applied to the cell bodies of primary afferent neurons located within the dorsal root ganglia (DRG) (Jahr and Jessell, 1983). The depolarizing effect of ATP results from the activation of a non-selective cation channel (Bean, 1990) and is blocked by P2 purinoreceptor antagonists (Tsuda et al., 1999), indicating that excitation is mediated via ionotropic P2X purinoreceptors. 

Adenosine 5 -triphosphate is an excitatory neurotransmitter in the CNS and the peripheral nervous system (PNS). ATP acts via ionotropic P2X receptors (Chapter 3) and also acts through metabotropic G protein-linked P2Y receptors. With respect to P2Y receptors 1-13 that have been distinguished, uridine 5 -triphosphate (UTP) and ATP bind to P2Y2 and P2Y4 and ATP also binds to P2Y11. The signalling mechanism involves Gaq-mediated cytosolic Ca2+ elevation. 

P2X7 (P2Z ATP ) receptors show an order of potency where A TP is active, but ADP or AMP is inactive dBz-ATP (2, 3 -0-di (benzoyl)-adenosine triphosphate) is a relatively selective agonist. Many immune and inflammatory cells express these receptors which appear to be coupled in some way to plasma membrane pores. It was not initially evident that these receptors fell into the P2X ionotropic group, and... 

ATP coreleased with ACh mediates fast excitation by acting on postsynaptic ionotropic P2X2-P2X3 purinergic receptors on afferent nerve terminal, and consequently a ventilatory response to hypoxia (Spyer et al., 2004). 

Soto, F., Garcia-Guzman, M., Gomez-Hernandez, J.M., Hollmann, M., Karschin, C., and Stiihmer, W. (1996) P2X4 An ATP-activated ionotropic receptor cloned from rat brain. Proc.Natl.Acad.Sci.USA, 93 3684-3688. 

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