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Article: Diadenosine polyphosphate analog controls postsynaptic excitation in CA3-CA1 synapses via a nitric oxide-dependent mechanism

TitleDiadenosine polyphosphate analog controls postsynaptic excitation in CA3-CA1 synapses via a nitric oxide-dependent mechanism
Authors
Issue Date2006
PublisherAmerican Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://jpet.aspetjournals.org
Citation
Journal Of Pharmacology And Experimental Therapeutics, 2006, v. 318 n. 2, p. 579-588 How to Cite?
AbstractPreviously, we have described the modulatory effect of diadenosine polyphosphates Ap4A and Ap5A on synaptic transmission in the rat hippocampal slices mediated by presynaptic receptors (Klishin et al., 1994). In contrast, we now describe how nonhydrolyzable Ap4A analog diadenosine-5′,5‴-P1,P4-[β, β′-methylene]tetraphosphate (AppCH2ppA) at low micromolar concentrations exerts strong nondesensitizing inhibition of orthodromically evoked field potentials (OFPs) without affecting the amplitude of excitatory postsynaptic currents and antidromically evoked field potentials, as recorded in hippocampal CA1 zone. The effects of AppCH2ppA on OFPs are eliminated by a P2 receptor antagonist pyridoxal-phosphate-6-azophenyl-2′, 4′-disulfonic acid (PPADS) but not mimicked by purinoceptor agonists α,β-methylene-ATP and adenosine 5′-O-(3-thio)-triphosphate, indicating that a P2-like receptor is involved but not one belonging to the conventional P2X/P2Y receptor classes. Diadenosine polyphosphate receptor (P4) antagonist Ip4I (diinosine tetraphosphate) was unable to modulate AppCH2ppA effects. Thus, the PPADS-sensitive P2-like receptor for AppCH2ppA seems to control selectively dendritic excitation of the CA1 neurons. The specific nitric oxide (NO)-scavenger 2-phenyl-4,4,5,5- tetramethyl-imidazoline-1-oxyl-3-oxide is shown to significantly attenuate AppCH2ppA-mediated inhibitory effects, indicating that NO is involved in the cascade of events initiated by AppCH2ppA. Further downstream mediation by adenosine A1 receptors is also demonstrated. Hence, AppCH2ppA-mediated effects involve PPADS-sensitive P2-like receptor activation leading to the production of NO that stimulates intracellular synthesis of adenosine, causing in turn postsynaptic A1 receptor activation and subsequent postsynaptic CA1 dendritic inhibition. Such spatially selective postsynaptic dendritic inhibition may influence dendritic electrogenesis in pyramidal neurons and consequently mediate control of neuronal network activity. Copyright © 2006 by The American Society for Pharmacology and Experimental Therapeutics.
Persistent Identifierhttp://hdl.handle.net/10722/68038
ISSN
2015 Impact Factor: 3.76
2015 SCImago Journal Rankings: 1.847
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMelnik, Sen_HK
dc.contributor.authorWright, Men_HK
dc.contributor.authorTanner, JAen_HK
dc.contributor.authorTsintsadze, Ten_HK
dc.contributor.authorTsintsadze, Ven_HK
dc.contributor.authorMiller, ADen_HK
dc.contributor.authorLozovaya, Nen_HK
dc.date.accessioned2010-09-06T06:00:45Z-
dc.date.available2010-09-06T06:00:45Z-
dc.date.issued2006en_HK
dc.identifier.citationJournal Of Pharmacology And Experimental Therapeutics, 2006, v. 318 n. 2, p. 579-588en_HK
dc.identifier.issn0022-3565en_HK
dc.identifier.urihttp://hdl.handle.net/10722/68038-
dc.description.abstractPreviously, we have described the modulatory effect of diadenosine polyphosphates Ap4A and Ap5A on synaptic transmission in the rat hippocampal slices mediated by presynaptic receptors (Klishin et al., 1994). In contrast, we now describe how nonhydrolyzable Ap4A analog diadenosine-5′,5‴-P1,P4-[β, β′-methylene]tetraphosphate (AppCH2ppA) at low micromolar concentrations exerts strong nondesensitizing inhibition of orthodromically evoked field potentials (OFPs) without affecting the amplitude of excitatory postsynaptic currents and antidromically evoked field potentials, as recorded in hippocampal CA1 zone. The effects of AppCH2ppA on OFPs are eliminated by a P2 receptor antagonist pyridoxal-phosphate-6-azophenyl-2′, 4′-disulfonic acid (PPADS) but not mimicked by purinoceptor agonists α,β-methylene-ATP and adenosine 5′-O-(3-thio)-triphosphate, indicating that a P2-like receptor is involved but not one belonging to the conventional P2X/P2Y receptor classes. Diadenosine polyphosphate receptor (P4) antagonist Ip4I (diinosine tetraphosphate) was unable to modulate AppCH2ppA effects. Thus, the PPADS-sensitive P2-like receptor for AppCH2ppA seems to control selectively dendritic excitation of the CA1 neurons. The specific nitric oxide (NO)-scavenger 2-phenyl-4,4,5,5- tetramethyl-imidazoline-1-oxyl-3-oxide is shown to significantly attenuate AppCH2ppA-mediated inhibitory effects, indicating that NO is involved in the cascade of events initiated by AppCH2ppA. Further downstream mediation by adenosine A1 receptors is also demonstrated. Hence, AppCH2ppA-mediated effects involve PPADS-sensitive P2-like receptor activation leading to the production of NO that stimulates intracellular synthesis of adenosine, causing in turn postsynaptic A1 receptor activation and subsequent postsynaptic CA1 dendritic inhibition. Such spatially selective postsynaptic dendritic inhibition may influence dendritic electrogenesis in pyramidal neurons and consequently mediate control of neuronal network activity. Copyright © 2006 by The American Society for Pharmacology and Experimental Therapeutics.en_HK
dc.languageengen_HK
dc.publisherAmerican Society for Pharmacology and Experimental Therapeutics. The Journal's web site is located at http://jpet.aspetjournals.orgen_HK
dc.relation.ispartofJournal of Pharmacology and Experimental Therapeuticsen_HK
dc.subject.meshAdenosine - pharmacologyen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshCyclic N-Oxides - pharmacologyen_HK
dc.subject.meshDendrites - drug effectsen_HK
dc.subject.meshDinucleoside Phosphates - pharmacologyen_HK
dc.subject.meshElectric Stimulationen_HK
dc.subject.meshElectrophysiologyen_HK
dc.subject.meshExcitatory Postsynaptic Potentials - drug effectsen_HK
dc.subject.meshHippocampus - cytology - drug effectsen_HK
dc.subject.meshHydrolysisen_HK
dc.subject.meshImidazoles - pharmacologyen_HK
dc.subject.meshNitric Oxide - physiologyen_HK
dc.subject.meshNitroglycerin - pharmacologyen_HK
dc.subject.meshPatch-Clamp Techniquesen_HK
dc.subject.meshPurinergic Agonistsen_HK
dc.subject.meshPurinergic Antagonistsen_HK
dc.subject.meshPyramidal Cells - drug effectsen_HK
dc.subject.meshPyridoxal Phosphate - analogs & derivatives - pharmacologyen_HK
dc.subject.meshRatsen_HK
dc.subject.meshRats, Wistaren_HK
dc.subject.meshSynaptic Transmission - drug effectsen_HK
dc.titleDiadenosine polyphosphate analog controls postsynaptic excitation in CA3-CA1 synapses via a nitric oxide-dependent mechanismen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-3565&volume=318&spage=579&epage=588&date=2006&atitle=Diadenosine+Polyphosphate+Analog+Controls+Postsynaptic+Excitation+in+CA3-CA1+Synapses+via+a+Nitric+Oxide-Dependent+Mechanism.en_HK
dc.identifier.emailTanner, JA:jatanner@hku.hken_HK
dc.identifier.authorityTanner, JA=rp00495en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1124/jpet.105.097642en_HK
dc.identifier.pmid16709679en_HK
dc.identifier.scopuseid_2-s2.0-33745946257en_HK
dc.identifier.hkuros120527en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33745946257&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume318en_HK
dc.identifier.issue2en_HK
dc.identifier.spage579en_HK
dc.identifier.epage588en_HK
dc.identifier.isiWOS:000239023100015-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridMelnik, S=14039513100en_HK
dc.identifier.scopusauthoridWright, M=11139776500en_HK
dc.identifier.scopusauthoridTanner, JA=35513993000en_HK
dc.identifier.scopusauthoridTsintsadze, T=6602181172en_HK
dc.identifier.scopusauthoridTsintsadze, V=14039705700en_HK
dc.identifier.scopusauthoridMiller, AD=7406230808en_HK
dc.identifier.scopusauthoridLozovaya, N=6701834046en_HK

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