P2 nucleotide receptors in peripheral nerve trunk

Abstract

There is considerable interest in the possibility that ATP may function as a peripheral pain mediator. Most of the studies underlying this idea are electrophysiological recordings from sensory cell bodies, as nociceptive axons with diameters of 1 to 3 µm are not accessible by intracellular electrophysiological methods. However, the most important region for conduction of nociceptive information is thin axons in the peripheral nerve trunk. These nociceptive axons are in close contact with ensheathing Schwann cells, which also cannot easily be studied in situ by conventional recording techniques. In this review, we describe new methods that have been used to study the effects of ATP on unmyelinated axons and Schwann cells in intact peripheral nerve preparations. Threshold tracking of compound C fibre potentials and confocal calcium imaging revealed that extracellular ATP has rapid excitatory effects on both axons and Schwann cells in peripheral nerve trunk. Thereby, at least four different ionotropic and metabotropic P2 receptors were separated by pharmacological profiles. These receptors (P2X 2/3 on unmyelinated axons; P2Y 1 , P2Y 2 , and P2X 7 on Schwann cells) would allow for rapid interactions between axons and Schwann cells. It is suggested that purinergic signalling in peripheral nerve trunk contributes not only to pain transduction but might be involved in mechanosensitivity, inflammation, proliferation, and demyelination. Drug Dev. Res. 52:83-88, 2001.

Pathophysiology and Therapeutic Potential of Purinergic Signaling

“…However, P2 receptors on oligodendrocytic progenitor cells mediate an increase in [Ca 2ϩ ] i and may mediate the formation of myelin, raising the possibility that activation of P2 receptors may offer new approaches to the treatment of demyelinating diseases in the CNS, such as multiple sclerosis Agresti et al, 2005). P2X receptors expressed by Schwann cells may regulate the synthesis and release of cytokines during pathophysiological events (Colomar and Amedee, 2001;Irnich et al, 2001). …”

Structure−Activity Relationship Studies on a Series of Novel, Substituted 1-Benzyl-5-phenyltetrazole P2X7Antagonists

“…[7][8][9] P2X 7 is expressed in the periphery on cells of the immune system such as macrophages and epidermal Langerhans cells. 6 The receptor is also expressed in the central nervous system on microglia 10 and astrocytes, 11 although the presence of P2X 7 on neurons remains controversial. 12 Brief activation of P2X 7 by extracellular ATP initiates a complex sequence of events, including ion influx, 13 caspase-1 activation, 14 release of the proinflammatory cytokine IL-1β, 15,16 and p38 MAP kinase activation.…”

Mitogen-Activated Protein Kinase and Caspase Signaling Pathways Are Required for P2X7Receptor (P2X7R)-Induced Pore Formation in Human THP-1 Cells

“…P2X 7 Rs are uniquely expressed on macrophages, epidermal Langerhans cells, and other antigen-presenting cells (Surprenant et al, 1996). Within the central nervous system, P2X 7 R expression has been reported on microglia (Ferrari et al, 1996), astrocytes, Schwann cells (Irnich et al, 2001), and presynaptic neuronal terminals in hippocampus and spinal cord (Duechars et al, 2001).…”