ATP as a presynaptic modulator

Abstract

There is considerable evidence that ATP acts as a fast transmitter or co-transmitter in autonomic and sensory nerves mostly through activation of ionotropic P2X receptors but also through metabotropic P2Y receptors. By analogy, the observations that ATP is released from stimulated central nervous system (CNS) nerve terminals and that responses to exogenously added ATP can be recorded in central neurons, lead to the proposal that ATP might also be a fast transmitter in the CNS. However, in spite of the robust expression of P2 receptor mRNA and binding to P2 receptors in the CNS, the demonstration of central purinergic transmission has mostly remained elusive. We now review evidence to suggest that ATP may also act presynaptically rather than solely postsynaptically in the nervous system.

Purinergic and Vanilloid Receptor Activation Releases Glutamate from Separate Cranial Afferent Terminals in Nucleus Tractus Solitarius

“…VR1 and P2X receptors are coupled to poorly selective cation channels with relatively large Ca 2ϩ permeabilities (Szallasi and Blumberg, 1999;Burnstock, 2000;Cunha and Ribeiro, 2000;Caterina and Julius, 2001;Khakh, 2001;Egan and Khakh, 2004;Shigetomi and Kato, 2004). Agonist activation of either receptor will depolarize presynaptic terminals, and this will activate voltage-dependent Na ϩ and Ca 2ϩ channels in the terminals.…”

Neuronal Activity Regulates Correlated Network Properties of Spontaneous Calcium Transients in AstrocytesIn Situ

“…Because ATP signaling is a relevant extracellular messenger that activates astrocytes (Fields and Stevens, 2000), we evaluated the participation of purinergic receptors in the generation of spontaneous [Ca 2ϩ ] i oscillations by blocking P2 receptors with the antagonist suramin (100 M) in the presence of TTX (2 M) to block suramin effects on neurons (Cunha and Ribeiro, 2000). Again, the proportion of spontaneously active astrocytes was not altered significantly under these conditions (Fig.…”

Neuroprotective roles of the P2Y2 receptor

“…The role of P1 and P2 receptors in the function of immune cells (e.g., neutrophils, eosinophils, monocytes, macrophages, mast cells, and lymphocytes) has been well described [26,[52][53][54][55][56][57], and the studies suggest that these receptors regulate cellular responses associated with inflammatory diseases. P2Rs are expressed at presynaptic nerve terminals where P2X1, P2X2, and P2X3 receptors have facilitatory, whereas P2Y 1 , P2Y 2 , and P2Y 4 receptors have inhibitory roles in synaptic transmission [10,[58][59][60][61][62]. Studies also have shown that postsynaptic P2 receptors including P2X3, P2Y 4 , and P2Y 1 receptors are involved in neuromodulation [10,[63][64][65], where they regulate either transmitter release or postsynaptic sensitivity to other neurotransmitters.…”