A new class of ligand-gated ion channel defined by P2X receptor for extracellular ATP

Valera, Soledad; Hussy, Nicolas; Evans, Richard J.; Adami, Nadia; North, Richard; Surprenant, Annmarie; Buell, Gary

doi:10.1038/371516a0

Cited by 978 publications

(725 citation statements)

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“…2A). This P2X isoform showed a more restricted mRNA expression pattern than those observed for P2X1, P2X2 and P2X4 receptors [5,6,9,12,13]. Transcripts were detected only in a few major tissues, namely brain, heart, spinal cord and adrenal gland.…”

Section: Tissue Distribution Of P2x5 Mrna Expressionmentioning

confidence: 74%

“…All these effects are apparently mediated by a miscellaneous group of G-protein coupled receptors (P2Y) and ligand-gated channels (P2X) [4]. To date, despite the numerous functions attributed to extracellular ATP, only four P2X receptors have been identified: P2X1 [5], P2X2 [6], P2X3 [7,8] and P2X4 [9][10][11][12][13]. Analysis of the amino acid sequences provides evidence of a novel family of membrane proteins consisting of two short intracellular domains, two transmembrane-spanning motifs, and a large extracellular loop comprising 10 conserved cysteines.…”

Section: Introductionmentioning

confidence: 99%

“…Analysis of P2X mRNA expression reveals a broad distribution of P2X1, P2X2 and P2X4 transcripts throughout the major tissues of the body [5,6,9,12,13,15], indicating a role of these proteins in many different physiological actions. In contrast, P2X3 transcripts have a localization limited to nociceptive neurons corresponding to C-fibre afferents of dorsal root *Corresponding author.…”

Section: Introductionmentioning

confidence: 99%

“…Heterologous expression of each recombinant P2X isoform results in ATP-activated cation-selective channels with diverse pharmacological and desensitization phenotypes [5][6][7][8][9][10][11][12][13]17]. The main pharmacological distinction is their the relative sensitivities to the agonist a,13-meATP and the antagonists suramin and PPADS.…”

Section: Introductionmentioning

confidence: 99%

“…The main pharmacological distinction is their the relative sensitivities to the agonist a,13-meATP and the antagonists suramin and PPADS. Thus, a,13-meATP is a full agonist for P2X1 and P2X3 receptors [5,7,8,17], but is not effective on the P2X2 and P2X4 forms [9][10][11][12][13]17]. On the other hand, P2X4 is the only purinergic receptor cloned so far that is insensitive to the established P2X blockers suramin and PPADS [9,10,12,13].…”

Section: Introductionmentioning

confidence: 99%

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Molecular cloning and functional expression of a novel rat heart P2X purinoceptor

et al. 1996

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Here we describe a novel purinergic receptor, the P2X5 receptor, cloned from rat heart. The full-length cDNA encodes a protein 455 amino acids long which shares an overall identity of 40-47% with other members of the P2X purinergic receptor family. P2X5 mRNA transcripts are found predominantly in rat heart but are also present in brain, spinal cord and adrenal gland. Functional expression of the recombinant receptor in HEK-293 cells shows a current that resembles mostly the P2X2 phenotype: the ATP-activated current reveals little agonist desensitization, is not activated by a,~meATP and is completely blocked by suramin and PPADS.

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Section: Tissue Distribution Of P2x5 Mrna Expressionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Molecular cloning and functional expression of a novel rat heart P2X purinoceptor

et al. 1996

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Localization of mRNA encoding the P2X2 receptor subunit of the adenosine 5?-triphosphate-gated ion channel in the adult and developing rat inner ear by in situ hybridization

1998

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Localization of expression of the adenosine 5'-triphosphate (ATP)-gated ion channel P2X2 receptor subunit (P2X2R) in the rat inner ear at different stages of development was achieved by using in situ mRNA hybridization. In the adult, P2X2R mRNA was strongly expressed in many of the cells bordering the cochlear endolymphatic compartment. This included the interdental cells of the spiral limbus, all cells of the inner sulcus and organ of Corti, and cells of the spiral prominence. In the vestibular labyrinth, strong expression was noted in the transitional cells at the base of the crista ampullaris and in the sensory epithelium of the crista and maculae. During development, P2X2R mRNA expression was evident in the precursors of these structures at the earliest period studied, embryonic day 12 (E12). Expression increased during the ontogeny in both the cochlear and the vestibular end organs. In addition, both the spiral and vestibular ganglia showed developmental expression. In contrast to the supporting cells of the organ of Corti, both inner and outer hair cells exhibited P2X2R mRNA only after postnatal day 10 (P10) through P12, concomitant with the onset of hearing. P2X2R expression levels in all cells fell from a maximum at P12-P18 to lower levels in the adult. In the adult, P2X2R mRNA levels were modest in outer hair cells in the basal (high-frequency) encoding region of the cochlea, and inner hair cell labeling was low throughout the cochlea. Reissner's membrane, which maintains an electrochemical barrier between scala vestibuli and scala media, showed considerable expression of P2X2R mRNA in early postnatal development, and expression was maintained at moderate levels in the adult cochlea. These data are consistent with a role for the P2X2R subunit in the processes of labyrinthine development and the regulation of the electrochemical gradients supporting auditory and vestibular sensory transduction.

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Distribution of the P2X2 receptor subunit of the ATP-gated ion channels in the rat central nervous system

et al. 1999

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The distribution of the P2X2 receptor subunit of the adenosine 5′‐triphosphate (ATP)‐gated ion channels was examined in the adult rat central nervous system (CNS) by using P2X2 receptor‐specific antisera and riboprobe‐based in situ hybridisation. P2X2 receptor mRNA expression matched the P2X2 receptor protein localisation. An extensive expression pattern was observed, including: olfactory bulb, cerebral cortex, hippocampus, habenula, thalamic and subthalamic nuclei, caudate putamen, posteromedial amygdalo‐hippocampal and amygdalo‐cortical nuclei, substantia nigra pars compacta, ventromedial and arcuate hypothalamic nuclei, supraoptic nucleus, tuberomammillary nucleus, mesencephalic trigeminal nucleus, dorsal raphe, locus coeruleus, medial parabrachial nucleus, tegmental areas, pontine nuclei, red nucleus, lateral superior olive, cochlear nuclei, spinal trigeminal nuclei, cranial motor nuclei, ventrolateral medulla, area postrema, nucleus of solitary tract, and cerebellar cortex. In the spinal cord, P2X2 receptor expression was highest in the dorsal horn, with significant neuronal labeling in the ventral horn and intermediolateral cell column. The identification of extensive P2X2 receptor immunoreactivity and mRNA distribution within the CNS demonstrated here provides a basis for the P2X receptor antagonist pharmacology reported in electrophysiological studies. These data support the role for extracellular ATP acting as a fast neurotransmitter at pre‐ and postsynaptic sites in processes such as sensory transmission, sensory‐motor integration, motor and autonomic control, and in neuronal phenomena such as long‐term potentiation (LTP) and depression (LTD). Additionally, labelling of neuroglia and fibre tracts supports a diverse role for extracellular ATP in CNS homeostasis. J. Comp. Neurol. 407:11–32, 1999. © 1999 Wiley‐Liss, Inc.

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A new class of ligand-gated ion channel defined by P2X receptor for extracellular ATP

Cited by 978 publications

References 28 publications

Molecular cloning and functional expression of a novel rat heart P2X purinoceptor

Molecular cloning and functional expression of a novel rat heart P2X purinoceptor

Localization of mRNA encoding the P2X2 receptor subunit of the adenosine 5?-triphosphate-gated ion channel in the adult and developing rat inner ear by in situ hybridization

Distribution of the P2X2 receptor subunit of the ATP-gated ion channels in the rat central nervous system

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