Purine Ionotropic (P2X) Receptors

Abstract

Purinergic signaling is involved in the proper functioning of virtually all organs of the body. Although in some cases purines have a major influence on physiological functions (e.g. thrombocyte aggregation), more often they are just background modulators contributing to fine tuning of biological events. However, under pathological conditions, when a huge amount of adenosine 5'-triphosphate (ATP) can reach the extracellular space, their significance is increasing. ATP and its various degradation products activate membrane receptors divided into two main classes: the metabotropic P2Y and the ionotropic P2X family. This latter group, the purine ionotropic receptor, is the object of this review. After providing a description about the distribution and functional properties of P2X receptors in the body, their pharmacology will be summarized. In the second part of this review, the role of purines in those organ systems and body functions will be highlighted, where the (patho)physiological role of P2X receptors has been suggested or is even well established. Besides the regulation of organ systems, for instance in the cardiovascular, respiratory, genitourinary or gastrointestinal system, some special issues will also be discussed, such as the role of P2X receptors in pain, tumors, central nervous system (CNS) injury and embryonic development. Several examples will indicate that purine ionotropic receptors might serve as attractive targets for pharmacological interventions in various diseases, and that selective ligands for these receptors will probably constitute important future therapeutic tools in humans.

The nociceptive and anti-nociceptive effects of bee venom injection and therapy: A double-edged sword

“…P2X3 and P2Y1 are expressed mainly in primary nociceptive sensory neurons, implicating a particular role in the mediation of nociception (Burnstock, 2000; Chizh and Illes, 2001; Kennedy et al, 2003; North, 2003; Boeynaems et al, 2005; Kennedy, 2005; Koles et al, 2007; Sawynok, 2007; Wirkner et al, 2007). …”

Activation of P2X7 receptors in the midbrain periaqueductal gray of rats facilitates morphine tolerance

“…Adenosine 5′-triphosphate (ATP) is released by neuronal and nonneuronal cells (Koles et al, 2007); in addition to being an intracellular energy source, ATP is an important neurotransmitter or neuromodulator that activates cation-permeable ion channels (P2X receptors) and G-protein-coupled receptors (P2Y receptors) on the cell surface (Burnstock, 2006). The P2X 7 receptor subtype, an ATP-gated nonselective cation channel (Sperlagh et al, 2006), is widely distributed in vivo, and its expression is altered in many pathophysiological processes, such as inflammation, pain, and cancer (Alves et al, 2013;Di Virgilio, 2012;Franceschini and Adinolfi, 2014).…”

Differential membrane redistribution of P2X receptor isoforms in response to osmotic and hyperglycemic stress in the rat lens

“…There are seven isoforms of P2X receptors (P2X 1-7 ) cloned in mammals to date, and these isoforms are widely expressed in virtually all tissues (North 2002;Burnstock 2004). Their biological role varies from modulation of neuronal transmission, muscle contraction, and immune cell responses (Koles et al 2007). An interesting feature of P2X receptors is their dynamic expression in diVerent tissues under both pathological conditions and during development.…”