Cited by 41Adenosine and Purinergic SignalingNeuroscience and Neuropharmacology ResearchPain Mechanisms and Treatments

P2X Receptor Activation Elicits Transporter-Mediated Noradrenaline Release from Rat Hippocampal Slices

Papp, Lilla, Balázsa, Tamás, Köfalvi, Attila, Erdélyi, Ferenc, Szabó, Gábor, Vizi, E. Sylvester, Sperlágh, Beáta·2004·The Journal of Pharmacology and Experimental Therapeutics

Abstract

This study was designed to test the hypothesis of whether activation of presynaptic P2X receptor-gated ion channels elicits noradrenaline release from central catecholaminergic terminals. ATP, alpha,beta-methylene-adenosine 5'-triphosphate (alpha,beta-methyleneATP), and ADP elicited concentration-dependent [3H]noradrenaline outflow from superfused rat hippocampal slices with the following rank order of agonist potency: alpha,beta-methyleneATP > ATP > ADP. Among P2 receptor antagonists, pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (30 microM), 4,4',4",4"'-[carbonylbis(imino-5,1,3-benzenetriyl-bis(carbonylimino))]tetrakis-1,3-benzenedisulfonic acid (100 nM), and 8,8'-[carbonybis(imino-3,1-phenylenecarbonylimino)]bis1,3,5-naphthalenetrisulphonic acid (10 microM) significantly inhibited the outflow of [3H]noradrenaline, evoked by ATP, whereas Brilliant Blue G (100 nM), 2'-deoxy-N6-methyladenosine 3',5'-bisphosphate tetraammonium (10 microM), the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (250 nM), and the A2A receptor antagonist 3,7-dimethyl-1-propargylxanthine (250 nM) were ineffective. Pretreatment with the Gi protein inhibitor pertussis toxin (2.5 microg/ml) did not change the effect of ATP on [3H]noradrenaline outflow. In contrast, a decrease in extracellular pH from 7.4 to 6.6 significantly attenuated the response by ATP. When extracellular Na+ was replaced by choline chloride and in the presence of the noradrenaline uptake inhibitor desipramine (10 microM), the ATP-evoked [3H]noradrenaline outflow was almost completely abolished, indicating that its underlying mechanism is the sodium-dependent reversal of the noradrenaline transporter. Reverse transcription-polymerase chain reaction analysis revealed that mRNA encoding P2X1, P2X2, P2X3, P2X4, P2X6, P2X7 and P2Y1 receptor subunits were expressed in the brainstem containing catecholaminergic nuclei projecting to the hippocampus, whereas mRNA encoding P2X5, P2Y2, P2Y4, and P2Y6 receptors were absent. Taken together, these results indicate that noradrenergic terminals of the rat hippocampus are equipped with presynaptic facilitatory P2X receptors, displaying a pharmacological profile similar to homomeric P2X1 and P2X3 receptors.

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Crossref · 10.1124/jpet.104.066712

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  • P2XR stimulation elicits transporter-mediated NA release from rat hippocampal slices.

    “P2XR stimulation also elicits transporter-mediated NA release from rat hippocampal slices [21], although the physiological relevance of this mechanism is not yet fully understood.”

    From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [21]

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Authors
Papp, L., Balázsa, T., Köfalvi, A., Erdélyi, F., Szabó, G., Vizi, E. S., & Sperlágh, B.
Affiliations
  • HUN-REN Institute of Experimental Medicine (HU)
  • Hungarian Academy of Sciences (HU)
Venue
The Journal of Pharmacology and Experimental Therapeutics
Publisher
Elsevier BV
Published
2004-09
Volume
310
Issue
3
Pages
973-980
ISSN
0022-3565 (ISSN-L)
OpenAlex
W2116991926
Cited by
41
References
42
Citations by year
2025: 1 · 2024: 3 · 2023: 2 · 2021: 2 · 2019: 2 · 2018: 1 · 2016: 1 · 2015: 2 · 2014: 1 · 2013: 3 · 2012: 3
FWCI
2.09
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Keywords
noradrenaline release, presynaptic neurotransmitter release, ATP, ADP, norepinephrine transporter, hippocampus, purinergic signaling, extracellular pH, sodium dependence, P2X receptor antagonists, pertussis toxin, desipramine, norepinephrine reuptake inhibition, Gi protein signaling
MeSH terms
Animals, Chromatography, High Pressure Liquid, Hippocampus, Male, Norepinephrine, RNA, Messenger, Rats, Wistar, Receptors, Purinergic P2, Reverse Transcriptase Polymerase Chain Reaction, Rats, Receptors, Purinergic P2X

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