Activation of Astrocytic μ-opioid Receptor Elicits Fast Glutamate Release Through TREK-1-Containing K2P Channel in Hippocampal Astrocytes
| Autor: | Dong Ho Woo, Jin Young Bae, Min-Ho Nam, Heeyoung An, Yeon Ha Ju, Joungha Won, Jae Hyouk Choi, Eun Mi Hwang, Kyung-Seok Han, Yong Chul Bae, C. Justin Lee |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Agonist Cannabinoid receptor TREK-1 medicine.drug_class hippocampus glutamate Hippocampal formation lcsh:RC321-571 03 medical and health sciences chemistry.chemical_compound Cellular and Molecular Neuroscience 0302 clinical medicine astrocyte Opioid receptor mental disorders medicine polycyclic compounds lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Original Research Glutamate receptor Adenosine receptor Cell biology DAMGO 030104 developmental biology medicine.anatomical_structure chemistry nervous system μ-opioid receptor human activities 030217 neurology & neurosurgery Astrocyte Neuroscience |
| Zdroj: | Frontiers in Cellular Neuroscience Frontiers in Cellular Neuroscience, Vol 12 (2018) |
| ISSN: | 1662-5102 |
| Popis: | Recently, μ-opioid receptor (MOR), one of the well-known Gi-protein coupled receptors (Gi-GPCR), was reported to be highly expressed in the hippocampal astrocytes. However, the role of astrocytic MOR has not been investigated. Here we report that activation of astrocytic MOR by [D-Ala2,N-MePhe4,Gly-ol]-enkephalin (DAMGO), a selective MOR agonist, causes a fast glutamate release using sniffer patch technique. We also found that the DAMGO-induced glutamate release was not observed in the astrocytes from MOR-deficient mice and MOR-short hairpin RNA (shRNA)-expressed astrocytes. In addition, the glutamate release was significantly reduced by gene silencing of the TREK-1-containing two-pore potassium (K2P) channel, which mediates passive conductance in astrocytes. Our findings were consistent with the previous study demonstrating that activation of Gi-GPCR such as cannabinoid receptor CB1 and adenosine receptor A1 causes a glutamate release through TREK-1-containing K2P channel from hippocampal astrocytes. We also demonstrated that MOR and TREK-1 are significantly co-localized in the hippocampal astrocytes. Furthermore, we found that both MOR and TREK-1-containing K2P channels are localized in the same subcellular compartments, soma and processes, of astrocytes. Our study raises a novel possibility that astrocytic MOR may participate in several physiological and pathological actions of opioids, including analgesia and addiction, through astrocytically released glutamate and its signaling pathway. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|