Localization of P2X and P2Y Receptors in Dorsal Root Ganglia of the Cat

Ruan, Han‐Li; Birder, Lori A.; Groat, William C. de; Tai, Changfeng; Roppolo, James R.; Buffington, C.A. Tony; Burnstock, Geoffrey

doi:10.1369/jhc.4a6556.2005

Cited by 41 publications

(25 citation statements)

References 60 publications

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“…In addition, we found that 64 % of P2X 3 receptor-expressing trigeminal ganglion neurons also express IB4, suggesting that they are mainly non-peptidergic, unmyelinated afferents, since IB4 labelling is almost entirely limited to non-peptide unmyelinated afferents in the rat (Ambalavanar and Morris, 1993;Kitchener et al, 1993;Kitchener et al, 1994;Stucky and Lewin, 1999;Gerke and Plenderleith, 2001). This proportion is in agreement with previous reports in the rat ( Vulchanova et al, 1998;Novakovic et al, 1999) and cat (88 %, Ruan et al, 2005). In rat DRG, P2X 3 is expressed by few (1-3 %) peptide containing neurons (Bradbury et al, 1998;Vulchanova et al, 1998).…”

Section: Discussion P2x 2 and P2x 3 Receptors Are Predominantly Locatsupporting

confidence: 93%

Localization of P2X2 and P2X3 receptors in rat trigeminal ganglion neurons

et al. 2007

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Purine receptors have been implicated in central neurotransmission from nociceptive primary afferent neurons, and adenosine 5'tri-phosphate (ATP)-mediated currents in sensory neurons have been shown to be mediated by both P2X 3 and P2X 2/3 receptors. The aim of the present study was to quantitatively examine the distribution of P2X 2 and P2X 3 receptors in primary afferent cell bodies in the rat trigeminal ganglion, including those innervating the dura. In order to determine the classes of neurons that express these receptor subtypes, purine receptor immunoreactivity was examined for colocalisation with markers of myelinated (neurofilament 200; NF200) or mostly unmyelinated, nonpeptidergic fibres (Bandeiraea simplicifolia isolectin B4; IB4). 40 % of P2X 2 and 64 % of P2X 3 receptor-expressing cells were IB4 positive, and 33 % of P2X 2 and 31 % of P2X 3 receptor-expressing cells were NF200 positive. Approximately 40 % of cells expressing P2X 2 receptors also expressed P2X 3 receptors and vice versa. Trigeminal ganglion neurons innervating the dura mater were retrogradely labelled and 52 % of these neurons expressed either P2X 2 or P2X 3 or both receptors. These results are consistent with electrophysiological findings that P2X receptors exist on the central terminals of trigeminal afferent neurons, and provide evidence that afferents supplying the dura express both receptors. In addition, the data suggest specific differences exist in P2X receptor expression between the spinal and trigeminal nociceptive systems. Keywords purine receptors; trigeminal ganglia; sensory neuron; migraine; pain Purine receptors have been widely implicated in nociceptive processing (Burnstock, 2000;Khakh, 2001;Liu and Salter, 2005). The receptors are of two types: ionotropic (P2X) and metabotropic (P2Y), both of which are stimulated by adenosine 5'tri-phosphate (ATP). Seven P2X receptor subtypes have been cloned, and some occur as heteromultimers (e.g. P2X 2/3 , P2X 1/5 and P2X 4/6 receptors). In the spinal somatosensory system, all P2X receptor subtypes with the exception of P2X 7 are expressed in the spinal dorsal horn, the dorsal root ganglion (DRG), and the central terminals of primary afferent neurons (Burnstock, 2000;Khakh, 2001;North, 2002). In vivo and in vitro electrophysiological recordings from single dorsal horn neurons have implicated P2X receptors on primary afferent terminals in spinal nociceptive transmission (Nakatsuka and Gu, 2001;Nakatsuka et al., 2002;Nakatsuka et al., 2003; Correspondence details: Dr. Ernest Jennings Dept. Anatomy & Cell Biology The University of Melbourne Parkville, Victoria, 3010, Australia Tel: +61 3 8344 5802 Fax: +61 3 9347 9619 Email: e.jennings@unimelb.edu.au. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form...

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Section: Discussion P2x 2 and P2x 3 Receptors Are Predominantly Locatsupporting

confidence: 93%

Localization of P2X2 and P2X3 receptors in rat trigeminal ganglion neurons

et al. 2007

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“…UTP is an agonist for P2Y 2 and P2Y 4 receptors [29]. P2Y 4 , a Gq-coupled UTP receptor, is expressed in sensory ganglia [33,34], but functional analysis shows low levels of P2Y 4 receptor expression in DRG neurons [8,35]. Suramin has been shown to block all nucleotide-sensitive P2Y receptors with the exception of the P2Y 4 receptor subtype [30].…”

Section: Discussionmentioning

confidence: 99%

Enhancement of acid-sensing ion channel activity by metabotropic P2Y UTP receptors in primary sensory neurons

Ren

Gan

et al. 2015

Purinergic Signalling

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Peripheral purinergic signaling plays an important role in nociception. Increasing evidence suggests that metabotropic P2Y receptors are also involved, but little is known about the underlying mechanism. Herein, we report that selective P2Y receptor agonist uridine 5′-triphosphate (UTP) can exert an enhancing effect on the functional activity of acidsensing ion channels (ASICs), key sensors for extracellular protons, in rat dorsal root ganglia (DRG) neurons. First, UTP dose-dependently increased the amplitude of ASIC currents. UTP also shifted the concentration-response curve for proton upwards, with a 56.6±6.4 % increase of the maximal current response to proton. Second, UTP potentiation of proton-gated currents can be mimicked by adenosine 5′-triphosphate (ATP), but not by P2Y1 receptor agonist ADP. Potentiation of UTP was blocked by P2Y receptor antagonist suramin and by inhibition of intracellular G protein, phospholipase C (PLC), protein kinase C (PKC), or protein interacting with C-kinase 1 (PICK1) signaling. Third, UTP altered acidosis-evoked membrane excitability of DRG neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acid stimuli. Finally, UTP dose-dependently exacerbated nociceptive responses to injection of acetic acid in rats. These results suggest that UTP enhanced ASIC-mediated currents and nociceptive responses, which reveal a novel peripheral mechanism underlying UTP-sensitive P2Y 2 receptor involvement in hyperalgesia by sensitizing ASICs in primary sensory neurons.

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“…Out of the population of DRG neurons that express CGRP, only 14-26% express P2X 3 (Bradbury et al, 1998;Ruan et al, 2005). In trigeminal neurons expressing CGRP, about 80% co-express P2X 3 (Fabbretti et al, 2006).…”

Section: Deep-tissue Craniofacial Peptidergic Afferent Neurons Co-expmentioning

confidence: 99%

Emerging Peripheral Receptor Targets for Deep-tissue Craniofacial Pain Therapies

Ambalavanar

Dessem

2009

J Dent Res

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While effective therapies are available for some types of craniofacial pain, treatments for deeptissue craniofacial pain such as temporomandibular disorders are less efficacious. Several ion channels and receptors which are prominent in craniofacial nociceptive mechanisms have been identified on trigeminal primary afferent neurons. Many of these receptors and channels exhibit unusual distributions compared with extracranial regions. For example, expression of the ATP receptor P2X 3 is strongly implicated in nociception and is more abundant on trigeminal primary afferent neurons than analogous extracranial neurons, making them potentially productive targets specifically for craniofacial pain therapies. The initial part of this review therefore focuses on P2X 3 as a potential therapeutic target to treat deep-tissue craniofacial pain. In the trigeminal ganglion, P2X 3 receptors are often co-expressed with the nociceptive neuropeptides CGRP and SP. Therefore, we discuss the role of CGRP and SP in deep-tissue craniofacial pain and suggest that neuropeptide antagonists, which have shown promise for the treatment of migraine, may have wider therapeutic potential, including the treatment of deep-tissue craniofacial pain. P2X 3 , TRPV1, and ASIC3 are often co-expressed in trigeminal neurons, implying the formation of functional complexes that allow craniofacial nociceptive neurons to respond synergistically to altered ATP and pH in pain. Future therapeutics for craniofacial pain thus might be more efficacious if targeted at combinations of P2X 3 , CGRP, TRPV1, and ASIC3.

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Localization of P2X and P2Y Receptors in Dorsal Root Ganglia of the Cat

Cited by 41 publications

References 60 publications

Localization of P2X2 and P2X3 receptors in rat trigeminal ganglion neurons

Localization of P2X2 and P2X3 receptors in rat trigeminal ganglion neurons

Enhancement of acid-sensing ion channel activity by metabotropic P2Y UTP receptors in primary sensory neurons

Emerging Peripheral Receptor Targets for Deep-tissue Craniofacial Pain Therapies

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