title: PGE2 Modulates GABAA Receptors via an EP1 Receptor-Mediated Signaling Pathway.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Wen-Hao
authors.initials: WH
authors.lastname: Dong
authors.forename: Chang-Long
authors.initials: CL
authors.lastname: Hu
authors.forename: Yan-Ai
authors.initials: YA
authors.lastname: Mei
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D015232:Dinoprostone / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology*; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D011963:Receptors, GABA-A; D058306:Receptors, Prostaglandin E, EP1 Subtype; D015232:Dinoprostone