PGE2 Modulates GABAA Receptors via an EP1 Receptor-Mediated Signaling Pathway
Aims: PGE2 is one of the most abundant prostanoids in mammalian tissues, but its effect on neuronal receptors has not been well investigated. This study examines the effect of PGE2 on GABAA receptor currents in rat cerebellar granule neurons. Methods: GABAA currents were recorded using a patch-clamp...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Cell Physiol Biochem Press GmbH & Co KG
2015-07-01
|
| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/430143 |
| _version_ | 1811197308719595520 |
|---|---|
| author | Guang Yang Wen-Hao Dong Chang-Long Hu Yan-Ai Mei |
| author_facet | Guang Yang Wen-Hao Dong Chang-Long Hu Yan-Ai Mei |
| author_sort | Guang Yang |
| collection | DOAJ |
| description | Aims: PGE2 is one of the most abundant prostanoids in mammalian tissues, but its effect on neuronal receptors has not been well investigated. This study examines the effect of PGE2 on GABAA receptor currents in rat cerebellar granule neurons. Methods: GABAA currents were recorded using a patch-clamp technique. Cell surface and total protein of GABAA β1/2/3 subunits was carried out by Western blot analysis. Results: Upon incubation of neurons with PGE2 (1 µM) for 60 minutes, GABAA currents were significantly potentiated. This PGE2-driven effect could be blocked by PKC or CaMKII inhibitors as well as EP1 receptor antagonist, and mimicked by PMA or EP1 receptor agonist. Furthermore, Western blot data showed that PGE2 did not increase the total expression level of GABAA receptors, but significantly increased surface levels of GABAA β1/2/3 subunits after 1 h of treatment. Consistently, both PKC and CaMKII inhibitors were able to reduce PGE2-induced increases in cell surface expression of GABAA receptors. Conclusion: Activation of either the PKC or CaMKII pathways by EP1 receptors mediates the PGE2-induced increase in GABAA currents. This suggests that upregulation of postsynaptic GABAA receptors by PGE2 may have profound effects on cerebellar functioning under physiological and pathological conditions. |
| first_indexed | 2024-04-12T01:11:50Z |
| format | Article |
| id | doaj.art-22a59db21abc45aa91ba8bcd95faf3e0 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-04-12T01:11:50Z |
| publishDate | 2015-07-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-22a59db21abc45aa91ba8bcd95faf3e02022-12-22T03:54:04ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-07-013651699171110.1159/000430143430143PGE2 Modulates GABAA Receptors via an EP1 Receptor-Mediated Signaling PathwayGuang YangWen-Hao DongChang-Long HuYan-Ai MeiAims: PGE2 is one of the most abundant prostanoids in mammalian tissues, but its effect on neuronal receptors has not been well investigated. This study examines the effect of PGE2 on GABAA receptor currents in rat cerebellar granule neurons. Methods: GABAA currents were recorded using a patch-clamp technique. Cell surface and total protein of GABAA β1/2/3 subunits was carried out by Western blot analysis. Results: Upon incubation of neurons with PGE2 (1 µM) for 60 minutes, GABAA currents were significantly potentiated. This PGE2-driven effect could be blocked by PKC or CaMKII inhibitors as well as EP1 receptor antagonist, and mimicked by PMA or EP1 receptor agonist. Furthermore, Western blot data showed that PGE2 did not increase the total expression level of GABAA receptors, but significantly increased surface levels of GABAA β1/2/3 subunits after 1 h of treatment. Consistently, both PKC and CaMKII inhibitors were able to reduce PGE2-induced increases in cell surface expression of GABAA receptors. Conclusion: Activation of either the PKC or CaMKII pathways by EP1 receptors mediates the PGE2-induced increase in GABAA currents. This suggests that upregulation of postsynaptic GABAA receptors by PGE2 may have profound effects on cerebellar functioning under physiological and pathological conditions.http://www.karger.com/Article/FullText/430143Cerebellar granule cellsEP receptorPKCPGE2GABAA receptors |
| spellingShingle | Guang Yang Wen-Hao Dong Chang-Long Hu Yan-Ai Mei PGE2 Modulates GABAA Receptors via an EP1 Receptor-Mediated Signaling Pathway Cellular Physiology and Biochemistry Cerebellar granule cells EP receptor PKC PGE2 GABAA receptors |
| title | PGE2 Modulates GABAA Receptors via an EP1 Receptor-Mediated Signaling Pathway |
| title_full | PGE2 Modulates GABAA Receptors via an EP1 Receptor-Mediated Signaling Pathway |
| title_fullStr | PGE2 Modulates GABAA Receptors via an EP1 Receptor-Mediated Signaling Pathway |
| title_full_unstemmed | PGE2 Modulates GABAA Receptors via an EP1 Receptor-Mediated Signaling Pathway |
| title_short | PGE2 Modulates GABAA Receptors via an EP1 Receptor-Mediated Signaling Pathway |
| title_sort | pge2 modulates gabaa receptors via an ep1 receptor mediated signaling pathway |
| topic | Cerebellar granule cells EP receptor PKC PGE2 GABAA receptors |
| url | http://www.karger.com/Article/FullText/430143 |
| work_keys_str_mv | AT guangyang pge2modulatesgabaareceptorsviaanep1receptormediatedsignalingpathway AT wenhaodong pge2modulatesgabaareceptorsviaanep1receptormediatedsignalingpathway AT changlonghu pge2modulatesgabaareceptorsviaanep1receptormediatedsignalingpathway AT yanaimei pge2modulatesgabaareceptorsviaanep1receptormediatedsignalingpathway |