The Signaling Pathways Involved in the Anticonvulsive Effects of the Adenosine A1 Receptor
Open Access
- 30 December 2020
- journal article
- review article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 22 (1), 320
- https://doi.org/10.3390/ijms22010320
Abstract
Adenosine acts as an endogenous anticonvulsant and seizure terminator in the brain. Many of its anticonvulsive effects are mediated through the activation of the adenosine A1 receptor, a G protein-coupled receptor with a wide array of targets. Activating A1 receptors is an effective approach to suppress seizures. This review gives an overview of the neuronal targets of the adenosine A1 receptor focusing in particular on signaling pathways resulting in neuronal inhibition. These include direct interactions of G protein subunits, the adenyl cyclase pathway and the phospholipase C pathway, which all mediate neuronal hyperpolarization and suppression of synaptic transmission. Additionally, the contribution of the guanyl cyclase and mitogen-activated protein kinase cascades to the seizure-suppressing effects of A1 receptor activation are discussed. This review ends with the cautionary note that chronic activation of the A1 receptor might have detrimental effects, which will need to be avoided when pursuing A1 receptor-based epilepsy therapies.Funding Information
- Fonds Wetenschappelijk Onderzoek (G042219N)
This publication has 202 references indexed in Scilit:
- Adenosine and its receptors as therapeutic targets: An overviewSaudi Pharmaceutical Journal, 2013
- Adenosinergic Depression of Glutamatergic Transmission in the Entorhinal Cortex of Juvenile Rats via Reduction of Glutamate Release Probability and the Number of Releasable VesiclesPLOS ONE, 2013
- GPCR mediated regulation of synaptic transmissionProgress in Neurobiology, 2012
- Phospholipase C signaling and calcium influxAdvances in Biological Regulation, 2012
- Two Distinct Aspects of Coupling between Gαi Protein and G Protein-activated K+ Channel (GIRK) Revealed by Fluorescently Labeled Gαi3 Protein SubunitsOnline Journal of Public Health Informatics, 2011
- Emerging roles for G protein-gated inwardly rectifying potassium (GIRK) channels in health and diseaseNature Reviews Neuroscience, 2010
- ERK activation causes epilepsy by stimulating NMDA receptor activityThe EMBO Journal, 2007
- Adenosine dysfunction in astrogliosis: cause for seizure generation?Neuron Glia Biology, 2007
- Purines, the carotid body and respirationRespiratory Physiology & Neurobiology, 2007
- Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockadePurinergic Signalling, 2005