Introduction and perspective, historical note

Burnstock, Geoffrey

doi:10.3389/fncel.2013.00227

Cited by 34 publications

(38 citation statements)

References 187 publications

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“…Most P2X subtypes are expressed in different regions of the central nervous system (CNS). P2X3, P2X2, P2X4, and P2X6 receptors are reported to be involved in neurotransmission and neuromodulation [17,18]. Several P2X subtypes, such as P2X2, P2X3, P2X4, and P2X7, are involved in the reflex activities of guts in rats [19,20].…”

Section: Introductionmentioning

confidence: 99%

Comparative study of the P2X gene family in animals and plants

Hou

Cao

2016

Purinergic Signalling

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P2X receptors are ligand-gated ion channels that can bind with the adenosine triphosphate (ATP) and have diverse functional roles in neuropathic pain, inflammation, special sense, and so on. In this study, 180 putative P2X genes, including 176 members in 32 animal species and 4 members in 3 species of lower plants, were identified. These genes were divided into 13 groups, including 7 groups in vertebrates and 6 groups in invertebrates and lower plants, through phylogenetic analysis. Their gene organization and motif composition are conserved in most predicted P2X members, while groupspecific features were also found. Moreover, synteny relationships of the putative P2X genes in vertebrates are conserved while simultaneously experiencing a series of gene insertion, inversion, and transposition. Recombination signals were detected in almost all of the vertebrates and invertebrates, suggesting that intragenic recombination may play a significant role in the evolution of P2X genes. Selection analysis also identified some positively selected sites that acted on the evolution of most of the predicted P2X proteins. The phenomenon of alternative splicing occurred commonly in the putative P2X genes of vertebrates. This article explored in depth the evolutional relationship among different subtypes of P2X genes in animal and plants and might serve as a solid foundation for deciphering their functions in further studies.

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Section: Introductionmentioning

confidence: 99%

Comparative study of the P2X gene family in animals and plants

Hou

Cao

2016

Purinergic Signalling

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“…As a neurotransmitter, ATP plays an important role in regulating the transduction of the visceral pain signal by binding to P2X receptors [15,16], and ATP participates in the regulation of intestinal movement and gastrointestinal secretion. P2X receptors are widely distributed in the body, and they play an important role in the formation, transduction, and regulation of neuropathic pain, inflammatory pain, and visceral pain [17][18][19][20]. Many studies have shown that purinergic (P2X) receptors are involved in pain signal transmission, in which the P2X 3 and P2X 2/3 receptors are the main subtypes [21,22].…”

Section: Introductionmentioning

confidence: 99%

Effect of electroacupuncture on P2X3 receptor regulation in the peripheral and central nervous systems of rats with visceral pain caused by irritable bowel syndrome

Weng

Wu²,

Zhou

et al. 2015

Purinergic Signalling

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The aim of this study is to investigate the role of the purinergic receptor P2X 3 in the peripheral and central nervous systems during acupuncture treatment for the visceral pain of irritable bowel syndrome (IBS). A total of 24 8-day-old Sprague-Dawley (SD) neonatal male rats (SPF grade) were stimulated using colorectal distention (CRD) when the rats were awake. The modeling lasted for 2 weeks with one stimulation per day. After 6 weeks, the rats were randomly divided into three groups of eight each: (1) the normal group (NG, n= 8); (2) the model group (MG, n=8); and (3) the model+ electroacupuncture group (EA, n = 8) that received electroacupuncture at a needling depth of 5 mm at the Shangjuxu (ST37, bilateral) and Tianshu (ST25, bilateral) acupoints. The parameters of the Han's acupoint nerve stimulator (HANS) were as follows: sparse-dense wave with a frequency of 2/100 Hz, current of 2 mA, 20 min/stimulation, and one stimulation per day; the treatment was provided for seven consecutive days. At the sixth week after the treatment, the abdominal withdrawal reflex (AWR) score was determined; immunofluorescence and immunohistochemistry were used to measure the expression of the P2X 3 receptor in myenteric plexus neurons, prefrontal cortex, and anterior cingulate cortex; and, a real-time PCR assay was performed to measure the expression of P2X 3 messenger RNA (mRNA) in the dorsal root ganglion (DRG) and spinal cord. After stimulation with CRD, the expression levels of the P2X 3 receptor in the intercolonic myenteric plexus, DRG, spinal cord, prefrontal cortex, and anterior cingulate cortex were upregulated, and the sensitivity of the rats to IBS visceral pain was increased. Electroacupuncture (EA) could downregulate the expression of the P2X 3 receptor and ease the sensitivity to visceral pain. The P2X 3 receptor plays an important role in IBS visceral pain. The different levels of P2X 3 in the peripheral enteric nervous system and central nervous system mediate the effects of the EA treatment of the visceral hyperalgesia of IBS.

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“…The P2X receptors are a family of cation channels gated by extracellular ATP (1,(7)(8)(9) and are involved in many physiological and pathophysiological processes (10)(11)(12). Seven subtypes of the P2X receptors have been identified in mammals (13), and they share ∼40% sequence identity.…”

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confidence: 99%

“…Each ligand for a ligand-gated ion channel has a distinct ability to evoke currents (1), and the ligands are classified according to the evoked current level: such as, full agonists, partial agonists, and antagonists. Partial agonists of ligand-gated ion channels reportedly offer clinical advantages over antagonists and full agonists in antidepressant and smoking-cessation treatment (2,3).…”

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confidence: 99%

Conductance of P2X ₄ purinergic receptor is determined by conformational equilibrium in the transmembrane region

Minato

Suzuki

Hara

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Ligand-gated ion channels are partially activated by their ligands, resulting in currents lower than the currents evoked by the physiological full agonists. In the case of P2X purinergic receptors, a cationselective pore in the transmembrane region expands upon ATP binding to the extracellular ATP-binding site, and the currents evoked by α,β-methylene ATP are lower than the currents evoked by ATP. However, the mechanism underlying the partial activation of the P2X receptors is unknown although the crystal structures of zebrafish P2X 4 receptor in the apo and ATP-bound states are available. Here, we observed the NMR signals from M339 and M351, which were introduced in the transmembrane region, and the endogenous alanine and methionine residues of the zebrafish P2X 4 purinergic receptor in the apo, ATP-bound, and α,β-methylene ATP-bound states. Our NMR analyses revealed that, in the α,β-methylene ATP-bound state, M339, M351, and the residues that connect the ATP-binding site and the transmembrane region, M325 and A330, exist in conformational equilibrium between closed and open conformations, with slower exchange rates than the chemical shift difference (<100 s −1 ), suggesting that the small population of the open conformation causes the partial activation in this state. Our NMR analyses also revealed that the transmembrane region adopts the open conformation in the state bound to the inhibitor trinitrophenyl-ATP, and thus the antagonism is due to the closure of ion pathways, except for the pore in the transmembrane region: i.e., the lateral cation access in the extracellular region.NMR | membrane proteins | ligand-gated ion channels | insect cell expression system | purinergic receptors I n chemical neurotransmission, various neurotransmitters bind to ligand-gated ion channels expressed in the plasma membrane of postsynaptic cells, such as the NMDA, AMPA, and P2X receptors, leading to changes in membrane potential and the concentration of intracellular ions. Each ligand for a ligand-gated ion channel has a distinct ability to evoke currents (1), and the ligands are classified according to the evoked current level: such as, full agonists, partial agonists, and antagonists. Partial agonists of ligand-gated ion channels reportedly offer clinical advantages over antagonists and full agonists in antidepressant and smoking-cessation treatment (2, 3).Two mechanisms have been proposed for the partial activation of the ligand-gated ion channels: the equilibrium between the open and closed conformations and the distinct conformation of the partial agonist-bound states from the closed and open conformations (4, 5). In the crystal structures of the extracellular region of the AMPA receptor, in which the distances between the two extracellular domains are changed upon agonist binding, the interdomain distances in the partial agonist-bound states correlated with the conductance level, suggesting that the AMPA receptor adopts specific intermediately permeable conformations (4, 6).The P2X receptors are a family of cation channe...

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Introduction and perspective, historical note

Cited by 34 publications

References 187 publications

Comparative study of the P2X gene family in animals and plants

Comparative study of the P2X gene family in animals and plants

Effect of electroacupuncture on P2X3 receptor regulation in the peripheral and central nervous systems of rats with visceral pain caused by irritable bowel syndrome

Conductance of P2X ₄ purinergic receptor is determined by conformational equilibrium in the transmembrane region

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Introduction and perspective, historical note

Cited by 34 publications

References 187 publications

Comparative study of the P2X gene family in animals and plants

Comparative study of the P2X gene family in animals and plants

Effect of electroacupuncture on P2X3 receptor regulation in the peripheral and central nervous systems of rats with visceral pain caused by irritable bowel syndrome

Conductance of P2X 4 purinergic receptor is determined by conformational equilibrium in the transmembrane region

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Conductance of P2X ₄ purinergic receptor is determined by conformational equilibrium in the transmembrane region