Nucleotide homeostasis and purinergic nociceptive signaling in rat meninges in migraine-like conditions

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dc.authorid0000-0003-3203-9893en_US
dc.authorid0000-0001-9261-2634en_US
dc.authorid0000-0001-6684-7982en_US
dc.authorid0000-0002-3359-6918en_US
dc.authorid0000-0002-8631-9586en_US
dc.contributor.authorYegutkin, Gennady G.
dc.contributor.authorGuerrero-Toro, Cindy
dc.contributor.authorKılınç, Erkan
dc.contributor.authorKoroleva, Kseniya
dc.contributor.authorIshchenko, Yevheniia
dc.date.accessioned2021-06-23T19:43:08Z
dc.date.available2021-06-23T19:43:08Z
dc.date.issued2016
dc.departmentBAİBÜ, Tıp Fakültesi, Temel Tıp Bilimleri Bölümüen_US
dc.description.abstractExtracellular ATP is suspected to contribute to migraine pain but regulatory mechanisms controlling pro-nociceptive purinergic mechanisms in the meninges remain unknown. We studied the peculiarities of metabolic and signaling pathways of ATP and its downstream metabolites in rat meninges and in cultured trigeminal cells exposed to the migraine mediator calcitonin gene-related peptide (CGRP). Under resting conditions, meningeal ATP and ADP remained at low nanomolar levels, whereas extracellular AMP and adenosine concentrations were one-two orders higher. CGRP increased ATP and ADP levels in meninges and trigeminal cultures and reduced adenosine concentration in trigeminal cells. Degradation rates for exogenous nucleotides remained similar in control and CGRP-treated meninges, indicating that CGRP triggers nucleotide release without affecting nucleotide-inactivating pathways. Lead nitrate-based enzyme histochemistry of whole mount meninges revealed the presence of high ATPase, ADPase, and AMPase activities, primarily localized in the medial meningeal artery. ATP and ADP induced large intracellular Ca2+ transients both in neurons and in glial cells whereas AMP and adenosine were ineffective. In trigeminal glia, ATP partially operated via P2X7 receptors. ATP, but not other nucleotides, activated nociceptive spikes in meningeal trigeminal nerve fibers providing a rationale for high degradation rate of pro-nociceptive ATP. Pro-nociceptive effect of ATP in meningeal nerves was reproduced by alpha,beta-meATP operating via P2X3 receptors. Collectively, extracellular ATP, which level is controlled by CGRP, can persistently activate trigeminal nerves in meninges which considered as the origin site of migraine headache. These data are consistent with the purinergic hypothesis of migraine pain and suggest new targets against trigeminal pain.en_US
dc.identifier.doi10.1007/s11302-016-9521-8
dc.identifier.endpage574en_US
dc.identifier.issn1573-9538
dc.identifier.issn1573-9546
dc.identifier.issue3en_US
dc.identifier.pmid27369815en_US
dc.identifier.scopus2-s2.0-84976519050en_US
dc.identifier.scopusqualityQ3en_US
dc.identifier.startpage561en_US
dc.identifier.urihttps://doi.org/10.1007/s11302-016-9521-8
dc.identifier.urihttps://hdl.handle.net/20.500.12491/8700
dc.identifier.volume12en_US
dc.identifier.wosWOS:000383603600013en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorKılınç, Erkan
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.relation.ispartofPurinergic Signallingen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectTrigeminal Neuronsen_US
dc.subjectMeningesen_US
dc.subjectATPen_US
dc.subjectADPen_US
dc.subjectAMPen_US
dc.subjectAdenosineen_US
dc.subjectCGRPen_US
dc.subjectNTPDaseen_US
dc.subjectPainen_US
dc.subjectMigraineen_US
dc.titleNucleotide homeostasis and purinergic nociceptive signaling in rat meninges in migraine-like conditionsen_US
dc.typeArticleen_US

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