ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
p38 mitogen-activated protein kinase contributes to adenosine A1 receptor-mediated synaptic depression in area CA1 of the rat hippocampus.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 50 citations in OpenAlex.
- The Anti-Parkinsonian A2A Receptor Antagonist Istradefylline (KW-6002) Attenuates Behavioral Abnormalities, Neuroinflammation, and Neurodegeneration in Cerebral Ischemia: An Adenosinergic Signaling Link Between Stroke and Parkinson's Disease.International journal of molecular sciences · 2025Article
- Adenosine receptor signalling in Alzheimer's disease.Purinergic signalling · 2022Review
- Adenosine Signaling and Clathrin-Mediated Endocytosis of Glutamate AMPA Receptors in Delayed Hypoxic Injury in Rat Hippocampus: Role of Casein Kinase 2.Molecular neurobiology · 2021Article
- Cordycepin Ameliorates Synaptic Dysfunction and Dendrite Morphology Damage of Hippocampal CA1Frontiers in cellular neuroscience · 2021Article
- The Signaling Pathways Involved in the Anticonvulsive Effects of the Adenosine AInternational journal of molecular sciences · 2020Review
- Long-term adenosine A1 receptor activation-induced sortilin expression promotes α-synuclein upregulation in dopaminergic neurons.Neural regeneration research · 2020Article
- Neuroprotective Effects of Adenosine A1 Receptor Signaling on Cognitive Impairment Induced by Chronic Intermittent Hypoxia in Mice.Frontiers in cellular neuroscience · 2020Article
- Adenosine AFrontiers in synaptic neuroscience · 2020Article
- Temperoammonic Stimulation Depotentiates Schaffer Collateral LTP via p38 MAPK Downstream of Adenosine A1 Receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Adenosine A1 and A2A Receptors in the Brain: Current Research and Their Role in Neurodegeneration.Molecules (Basel, Switzerland) · 2017Review
- Protein phosphatase 2A activation attenuates inflammation in murine models of acute lung injury.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- A1 adenosine receptor attenuates intracerebral hemorrhage-induced secondary brain injury in rats by activating the P38-MAPKAP2-Hsp27 pathway.Molecular brain · 2016Article
- Adenosine A1 Receptor-Mediated Endocytosis of AMPA Receptors Contributes to Impairments in Long-Term Potentiation (LTP) in the Middle-Aged Rat Hippocampus.Neurochemical research · 2016Article
- The Role of cGMP on Adenosine A 1 Receptor-mediated Inhibition of Synaptic Transmission at the Hippocampus.Frontiers in pharmacology · 2016Article
- Status Epilepticus Enhances Depotentiation after Fully Established LTP in an NMDAR-Dependent but GluN2B-Independent Manner.Neural plasticity · 2016Article
- Prolonged adenosine A1 receptor activation in hypoxia and pial vessel disruption focal cortical ischemia facilitates clathrin-mediated AMPA receptor endocytosis and long-lasting synaptic inhibition in rat hippocampal CA3-CA1 synapses: differential regulation of GluA2 and GluA1 subunits by p38 MAPK and JNK.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Intracellular signaling MAPK pathway after cerebral ischemia-reperfusion injury.Neurochemical research · 2012Article
- Molecular mechanisms involved in depotentiation and their relevance to schizophrenia.Chonnam medical journal · 2012Article
- Inhibition of hippocampal synaptic activity by ATP, hypoxia or oxygen-glucose deprivation does not require CD73.PloS one · 2012Article
- Neuroprotective signaling pathways are modulated by adenosine in the anoxia tolerant turtle.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2011Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adenosine is arguably the most potent and widespread presynaptic modulator in the CNS, yet adenosine receptor signal transduction pathways remain unresolved. Here, we demonstrate a novel mechanism in which adenosine A1 receptor stimulation leads to p38 mitogen-activated protein kinase (MAPK) activation and contributes to the inhibition of synaptic transmission. Western blot analysis indicated that selective A1 receptor activation [with N6-cyclopentyladenosine (CPA)] resulted in rapid increases in phosphorylated p38 (phospho-p38) MAPK immunoreactivity in membrane fractions, and decreases in phospho-p38 MAPK in cytosolic fractions. Immunoprecipitation with a phospho-p38 MAPK antibody revealed constitutive association of this phosphoprotein with adenosine A1 receptors. Phospho-p38 MAPK activation by A1 receptor stimulation induced translocation of PP2a (protein phosphatase 2a) to the membrane. We then examined the actions of p38 MAPK activation in A1 receptor-mediated synaptic inhibition. Excitatory postsynaptic field potentials evoked in area CA1 of the rat hippocampus markedly decreased in response to adenosine (10 microM), the A1 receptor agonist CPA (40 nM), or a 5 min exposure to hypoxia. These inhibitory responses were mediated by A1 receptor activation because the selective antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine) (100 nM) prevented them. In agreement with the biochemical analysis, the selective p38 MAPK inhibitor SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole] (25 microM) blocked the inhibitory actions of A1 receptor activation, whereas both the inactive analog SB202474 [4-ethyl-2-(p-methoxyphenyl)-5-(4'-pyridyl)-1H-imidazole] (25 microM) and the ERK 1/2 (extracellular signal-regulated kinase 1/2) MAPK inhibitor PD98059 [2'-amino-3'-methoxyflavone] (50 microM) were ineffective. In contrast, the p38 MAPK inhibitors did not inhibit GABA(B)-mediated synaptic depression. These data suggest A1 receptor-mediated p38 MAPK activation is a crucial step underlying the presynaptic inhibitory effect of adenosine on CA3-CA1 synaptic transmission.
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