Cellular Distribution and Functions of P2 Receptor Subtypes in Different Systems

Abstract

This review is aimed at providing readers with a comprehensive reference article about the distribution and function of P2 receptors in all the organs, tissues, and cells in the body. Each section provides an account of the early history of purinergic signaling in the organ?cell up to 1994, then summarizes subsequent evidence for the presence of P2X and P2Y receptor subtype mRNA and proteins as well as functional data, all fully referenced. A section is included describing the plasticity of expression of P2 receptors during development and aging as well as in various pathophysiological conditions. Finally, there is some discussion of possible future developments in the purinergic signaling field.

Purinergic mechanisms in neuroinflammation: An update from molecules to behavior

“…All known subtypes of P2Y receptors are expressed in the CNS with variable distribution among different cell types (i.e. neurons, astrocytes, microglia, oligodendrocytes) (Burnstock and Knight, 2004). These receptors are activated during pathological conditions and participate in neuroinflammation in many different ways.…”

“…While P2Y 11 mRNA can be found in the nervous system (Burnstock and Knight, 2004), and these receptors are expressed on human immunocytes and regulate neurotrophil apoptosis (Communi et al, 1999;Vaughan et al, 2007), a potential immunomodulatory role in the CNS may also be hypothesized. P2Y 12 receptors are G i -coupled receptors and well-known as the target site of widely used antithrombotic drugs such as clopidogrel or ticagrelor, and are therefore of considerable interest to cardiovascular medicine.…”

Dynamic regulation of the P2X4 receptor in alveolar macrophages by phagocytosis and classical activation

“…Recently, highly selective and potent P2X 7 R antagonists have been identified [10] with one of these showing initial positive results in Phase II clinical trials for rheumatoid arthritis [11]. The case for P2X 4 R remains tentative, largely due to the absence of selective P2X 4 R antagonists and the complicating presence of P2X 7 R, which is generally co-expressed with P2X 4 R in macrophages and microglia [3]. P2X 4 R does not appear to couple to any of the same downstream signalling cascades as has been demonstrated for P2X 7 R but studies with P2X 4 R gene-deleted mice have revealed abrogation of tactile allodynia in animal models of inflammatory (formalin-induced) and neuropathic (nerve section) pain via yet-to-be identified alterations in microglial functions [12][13][14].…”

“…Purine receptors Introduction Extracellular ATP acts as a ''danger signal'' when it is released from cells during tissue damage and inflammation; it acts on metabotropic (G-protein coupled) P2Y and ionotropic (cation channel) P2X purinergic receptors to affect several inflammatory and immune responses [1,2]. There are seven members of the P2X receptor family (P2X 1-7 R) that show widespread distribution in both neuronal and non-neuronal tissues [3]. Two of these seven members, P2X 4 R and P2X 7 R, have generated increasing interest as potential anti-inflammatory drug targets [2,4,5].…”

“…Two of these seven members, P2X 4 R and P2X 7 R, have generated increasing interest as potential anti-inflammatory drug targets [2,4,5]. The case for P2X 7 R is now well established: Stimulation of P2X 7 R in activated monocytes, macrophages and microglia leads to rapid release of pro-inflammatory IL-1b and IL-18 cytokines, to phospholipase D activation and, if stimulation is sustained, to apopotosis [1,[3][4][5]. Classical activation of macrophages, generally induced by IFN-g and/or LPS, up-regulates P2X 7 R mRNA and protein levels and functional expression [6,7] and this correlates well with a role for P2X 7 R in bacterial killing [8,9].…”