PMID- 19428786 OWN - NLM STAT- MEDLINE DCOM- 20090715 LR - 20211020 IS - 1872-9754 (Electronic) IS - 0197-0186 (Print) IS - 0197-0186 (Linking) VI - 54 IP - 7 DP - 2009 Jun TI - Activation of EP2 prostanoid receptors in human glial cell lines stimulates the secretion of BDNF. PG - 439-46 LID - 10.1016/j.neuint.2009.01.018 [doi] AB - Prostaglandin E(2) (PGE(2)) is produced at high levels in the injured central nervous system, where it is generally considered a cytotoxic mediator of inflammation. The cellular actions of PGE(2) are mediated by G-protein signaling activated by prostanoid receptors termed EP(1), EP(2), EP(3) and EP(4). Recent studies have implicated the EP(2) prostanoid receptor to be in apparently conflicting roles promoting neuronal death in some model systems and the survival of neurons in others. Here we show that treatment of immortalized human microglia and CCF-STTG1 astrocytes with either PGE(2) or the EP(2) selective agonist butaprost stimulates the release of brain-derived neurotrophic factor (BDNF). Both cell lines express mRNA for the EP(2) receptor, whereas transcripts for the other subtypes are not detected. Pharmacological studies using PGE(2) and modulators of cyclic AMP signaling implicate this pathway in PGE(2)-stimulated BDNF release. These results indicate that EP(2) prostanoid receptor activation induces BDNF secretion through stimulation of cyclic AMP dependent signaling. Our findings provide a mechanism by which endogenous PGE(2) might contribute to either neurotoxicity or neuroprotection in the injured brain via the induction of BDNF release from microglial cells and astrocytes. FAU - Hutchinson, Anthony J AU - Hutchinson AJ AD - Program in Neuroscience, The University of Arizona, College of Pharmacy, Gould-Simpson 611, PO Box 210077, Tucson, AZ 85721, USA. FAU - Chou, Chih-Ling AU - Chou CL FAU - Israel, Davelene D AU - Israel DD FAU - Xu, Wei AU - Xu W FAU - Regan, John W AU - Regan JW LA - eng GR - R01 EY011291/EY/NEI NIH HHS/United States GR - R01 EY011291-10/EY/NEI NIH HHS/United States GR - EY11291/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20090206 PL - England TA - Neurochem Int JT - Neurochemistry international JID - 8006959 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Prostaglandin E) RN - E0399OZS9N (Cyclic AMP) RN - EC 1.13.12.- (Luciferases) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) RN - EC 4.6.1.1 (Adenylyl Cyclases) RN - F5TD010360 (Alprostadil) RN - HP16WVP23Y (butaprost) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Adenylyl Cyclases/metabolism MH - Alprostadil/analogs & derivatives/pharmacology MH - Astrocytes/metabolism MH - Blotting, Western MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cell Line MH - Cyclic AMP/biosynthesis MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Cyclic AMP-Dependent Protein Kinases/metabolism MH - Dinoprostone/*metabolism MH - Enzyme-Linked Immunosorbent Assay MH - Humans MH - Luciferases/genetics MH - Neuroglia/drug effects/*metabolism MH - RNA, Messenger/biosynthesis/genetics MH - Receptors, Prostaglandin E/*agonists MH - Transfection PMC - PMC2717006 MID - NIHMS111976 EDAT- 2009/05/12 09:00 MHDA- 2009/07/16 09:00 PMCR- 2010/06/01 CRDT- 2009/05/12 09:00 PHST- 2008/09/04 00:00 [received] PHST- 2008/12/27 00:00 [revised] PHST- 2009/01/22 00:00 [accepted] PHST- 2009/05/12 09:00 [entrez] PHST- 2009/05/12 09:00 [pubmed] PHST- 2009/07/16 09:00 [medline] PHST- 2010/06/01 00:00 [pmc-release] AID - S0197-0186(09)00034-5 [pii] AID - 10.1016/j.neuint.2009.01.018 [doi] PST - ppublish SO - Neurochem Int. 2009 Jun;54(7):439-46. doi: 10.1016/j.neuint.2009.01.018. Epub 2009 Feb 6.