P2Y receptors and pain transmission

Gerevich, Zoltán; Illéš, Peter

doi:10.1007/s11302-004-4740-9

Cited by 82 publications

(53 citation statements)

References 77 publications

(100 reference statements)

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“…For instance, although the activation of the uridine P2Y 2 receptor promotes CGRP release (Sanada et al, 2002), and facilitates capsaicininduced currents in rat dorsal root ganglia (DRG) (Gerevich and Illes, 2004), UTP and UDP were found to be analgesic when intrathecally injected to rats (Okada et al, 2002). Moreover, neuronal P2Y 1 receptors can downregulate P2X 3 receptor function in rat DRG (Gerevich et al, 2005), and its cognate ligand ADP can exert an antinociceptive role (Gerevich and Illes, 2004). Conversely, the selective inhibition of the ADP-sensitive P2Y 12 receptor subtype in vivo significantly suppresses neuropathic pain following spinal nerve ligation (Tsuda et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Calcitonin Gene-Related Peptide-Mediated Enhancement of Purinergic Neuron/Glia Communication by the Algogenic Factor Bradykinin in Mouse Trigeminal Ganglia from Wild-Type and R192Q Ca_v2.1 Knock-In Mice: Implications for Basic Mechanisms of Migraine Pain

Ceruti¹,

Villa²,

Fumagalli³

et al. 2011

J. Neurosci.

114

131

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Within the trigeminal ganglion, crosstalk between neurons and satellite glial cells (SGCs) contributes to neuronal sensitization and transduction of painful stimuli, including migraine pain, at least partly through activation of purinergic receptor mechanisms. We previously showed that the algogenic mediator bradykinin (BK) potentiates purinergic P2Y receptors on SGCs in primary trigeminal cultures. Our present study investigated the molecular basis of this effect in wild-type (WT) mice and Ca V 2.1 ␣1 R192Q mutant knock-in (KI) mice expressing a human mutation causing familial hemiplegic migraine type 1. Single-cell calcium imaging of WT cultures revealed functional BK receptors in neurons only, suggesting a paracrine action by BK to release a soluble mediator responsible for its effects on SGCs. We identified this mediator as the neuropeptide calcitonin gene-related peptide (CGRP), whose levels were markedly increased by BK, while the CGRP antagonist CGRP 8-37 and the anti-migraine drug sumatriptan inhibited BK actions. Unlike CGRP, BK was ineffective in neuron-free SGC cultures, confirming the CGRP neuronal source. P2Y receptor potentiation induced by CGRP in SGCs was mediated via activation of the extracellular signal-regulated kinase 1/2 pathways, and after exposure to CGRP, a significant release of several cytokines was detected. Interestingly, both basal and BK-stimulated CGRP release was higher in KI mouse cultures, where BK significantly upregulated the number of SGCs showing functional UTP-sensitive P2Y receptors. Our findings suggest that P2Y receptors on glial cells might be considered as novel players in the cellular processes underlying migraine pathophysiology and might represent new targets for the development of innovative therapeutic agents against migraine pain.

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Section: Discussionmentioning

confidence: 99%

Calcitonin Gene-Related Peptide-Mediated Enhancement of Purinergic Neuron/Glia Communication by the Algogenic Factor Bradykinin in Mouse Trigeminal Ganglia from Wild-Type and R192Q Ca_v2.1 Knock-In Mice: Implications for Basic Mechanisms of Migraine Pain

Ceruti¹,

Villa²,

Fumagalli³

et al. 2011

J. Neurosci.

114

131

View full text Add to dashboard Cite

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“…Growing evidence suggests that nucleotides that are released upon injury or under physiological conditions stimulate nucleotide P2 receptors and serve as endogenous signals to induce a rapid response in glial cells [24][25][26]. Neurons and SCs in the PNS express purinergic receptors that are linked to the release of intracellular Ca 2+ stores and the regulation of several pathways [27][28][29][30].…”

Section: Discussionmentioning

confidence: 99%

N-cadherin expression is regulated by UTP in schwannoma cells

Martiáñez

Lamarca

Casals

et al. 2012

Purinergic Signalling

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Schwann cells (SCs) are peripheral myelinating glial cells that express the neuronal Ca 2+ -dependent cell adhesion molecule, neural cadherin (N-cadherin). Ncadherin is involved in glia-glia and axon-glia interactions and participates in many key events, which range from the control of axonal growth and guidance to synapse formation and plasticity. Extracellular UTP activates P2Y purinergic receptors and exerts short-and long-term effects on several tissues to promote wound healing. Nevertheless, the contribution of P2Y receptors in peripheral nervous system functions is not completely understood. The current study demonstrated that UTP induced a dose-and timedependent increase in N-cadherin expression in SCs. Furthermore, N-cadherin expression was blocked by the P2 purinoceptor antagonist suramin. The increased N-cadherin expression induced by UTP was mediated by phosphorylation of mitogen-activated protein kinases (MAPKs), such as Jun N-terminal kinase, extracellular-regulated kinase and p38 kinase. Moreover, the Rho kinase inhibitor Y27632, the phospholipase C inhibitor U73122 and the protein kinase C inhibitor calphostin C attenuated the UTP-induced activation of MAPKs significantly. Extracellular UTP also modulated increased in the expression of the early transcription factors c-Fos and c-Jun. We also demonstrated that the region of the N-cadherin promoter between nucleotide positions −3698 and −2620, which contained one activator protein-1-binding site, was necessary for UTP-induced gene expression. These results suggest a novel role for P2Y purinergic receptors in the regulation of N-cadherin expression in SCs.

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“…Messenger RNAs for P2Y 1,2,4,6,12,13,14 subtypes have been found in DRG neurons [30,31,32], suggesting that these receptors may play an ancillary role in peripheral somatosensory transmission [33,34]. P2Y receptors are located not only in the cell body, but also in peripheral and central terminals [35,36], where their activity is presumably integrated within the complex molecular network associated with the transmission of nociceptive signals to the CNS. Functional P2Y 1,2,4 receptors are also expressed in subsets of TG sensory neurons [30,37], but to date their role in the modulation of trigeminal pain has not been properly investigated.…”

Section: Modulation Of Pain Transmission By P2y Receptors In Sensory mentioning

confidence: 99%

P2Y purinergic receptors: New targets for analgesic and antimigraine drugs

Magni

Ceruti

2013

Biochemical Pharmacology

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Non-standard abbreviations:AR-C126313, 5-(7-chloro-4H-1-thia-3-aza-benzo[f]-4-yl)-3-methyl-6-thioxo-piperadin-2-one; AR-C67085, [[[[(2R,3S,4R,5R)-5-(6-amino-2-propylsulfanylpurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]-dichloromethyl]phosphonic acid; AR-C69931MX, [dichloro-[[[(2R,3S,4R,5R)-3,4-dihydroxy-5-[6-(2-methylsulfanylethylamino)-2-(3,3,3-trifluoropropylsulfanyl) 3-[7-[[2-(3,4-BDNF, brain-derived neurotrophic factor; BK, bradykinin; CFA, Complete Freund's adjuvant; CGRP, calcitonin gene-related peptide; DRG, dorsal root ganglia; FHM1, familial hemiplegic migraine type 1; INS37217, P(1)-(uridine 5')-P(4)-(2'-deoxycytidine 5')tetraphosphate, tetrasodium salt; INS48823, {[(3aR,4R,6R,6aR)-2-benzyl-6-(2,4-dioxo-

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P2Y receptors and pain transmission

Cited by 82 publications

References 77 publications

Calcitonin Gene-Related Peptide-Mediated Enhancement of Purinergic Neuron/Glia Communication by the Algogenic Factor Bradykinin in Mouse Trigeminal Ganglia from Wild-Type and R192Q Ca_v2.1 Knock-In Mice: Implications for Basic Mechanisms of Migraine Pain

Calcitonin Gene-Related Peptide-Mediated Enhancement of Purinergic Neuron/Glia Communication by the Algogenic Factor Bradykinin in Mouse Trigeminal Ganglia from Wild-Type and R192Q Ca_v2.1 Knock-In Mice: Implications for Basic Mechanisms of Migraine Pain

N-cadherin expression is regulated by UTP in schwannoma cells

P2Y purinergic receptors: New targets for analgesic and antimigraine drugs

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P2Y receptors and pain transmission

Cited by 82 publications

References 77 publications

Calcitonin Gene-Related Peptide-Mediated Enhancement of Purinergic Neuron/Glia Communication by the Algogenic Factor Bradykinin in Mouse Trigeminal Ganglia from Wild-Type and R192Q Cav2.1 Knock-In Mice: Implications for Basic Mechanisms of Migraine Pain

Calcitonin Gene-Related Peptide-Mediated Enhancement of Purinergic Neuron/Glia Communication by the Algogenic Factor Bradykinin in Mouse Trigeminal Ganglia from Wild-Type and R192Q Cav2.1 Knock-In Mice: Implications for Basic Mechanisms of Migraine Pain

N-cadherin expression is regulated by UTP in schwannoma cells

P2Y purinergic receptors: New targets for analgesic and antimigraine drugs

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Product

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Calcitonin Gene-Related Peptide-Mediated Enhancement of Purinergic Neuron/Glia Communication by the Algogenic Factor Bradykinin in Mouse Trigeminal Ganglia from Wild-Type and R192Q Ca_v2.1 Knock-In Mice: Implications for Basic Mechanisms of Migraine Pain

Calcitonin Gene-Related Peptide-Mediated Enhancement of Purinergic Neuron/Glia Communication by the Algogenic Factor Bradykinin in Mouse Trigeminal Ganglia from Wild-Type and R192Q Ca_v2.1 Knock-In Mice: Implications for Basic Mechanisms of Migraine Pain