PMID- 18384819 OWN - NLM STAT- MEDLINE DCOM- 20080722 LR - 20220317 IS - 0028-3908 (Print) IS - 0028-3908 (Linking) VI - 54 IP - 6 DP - 2008 May TI - Enhancement of long-term potentiation by brain-derived neurotrophic factor requires adenosine A2A receptor activation by endogenous adenosine. PG - 924-33 LID - 10.1016/j.neuropharm.2008.01.011 [doi] AB - The excitatory action of brain-derived neurotrophic factor (BDNF) on synaptic transmission is triggered by adenosine A2A receptor activation. Since high-frequency neuronal firing, such as that inducing long-term potentiation (LTP), favours both A2A receptor activation and BDNF effects on transmission, we now evaluated the influence of adenosine on the facilitatory action of BDNF upon CA1 hippocampal LTP. theta-Burst stimulation of the pyramidal inputs induced a significant and persistent increase in field EPSP slopes, and this potentiation was augmented in the presence of BDNF (20 ng/ml), an action prevented by the inhibitor of Trk receptor autophosphorylation, K252a (200 nM). Removal of endogenous extracellular adenosine with adenosine deaminase (ADA, 1 U/ml), as well as the antagonism of adenosine A2A receptors with SCH58261 (100 nM), prevented the excitatory action of BDNF upon LTP. In an adenosine depleted background (with ADA), activation of adenosine A2A receptors (with 10nM CGS21680) restored the facilitatory effect of BDNF on LTP; this was fully prevented by the protein kinase A inhibitor, H-89 (1 microM) and mimicked by the adenylate cyclase activator, forskolin (10 microM). In similar experiments, activation of adenosine inhibitory A1 receptors (with 5 nM CPA) did not affect the facilitatory effect of BDNF. In conclusion, the facilitatory action of BDNF upon hippocampal LTP is critically dependent on the presence of extracellular adenosine and A2A receptor activation through a cAMP/PKA-dependent mechanism. Since extracellular adenosine accumulates upon high-frequency neuronal firing, the present results reveal a key process to allow the influence of BDNF upon synaptic plasticity. FAU - Fontinha, B M AU - Fontinha BM AD - Institute of Pharmacology and Neurosciences, Faculty of Medicine and Unit of Neurosciences, Institute of Molecular Medicine, University of Lisbon, Av. Prof. Egas Moniz, 1649-028 Lisbon, Portugal. FAU - Diogenes, M J AU - Diogenes MJ FAU - Ribeiro, J A AU - Ribeiro JA FAU - Sebastiao, A M AU - Sebastiao AM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080208 PL - England TA - Neuropharmacology JT - Neuropharmacology JID - 0236217 RN - 0 (5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine) RN - 0 (Adenosine A2 Receptor Agonists) RN - 0 (Adenosine A2 Receptor Antagonists) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Carbazoles) RN - 0 (Indole Alkaloids) RN - 0 (Isoquinolines) RN - 0 (Neuroprotective Agents) RN - 0 (Phenethylamines) RN - 0 (Pyrimidines) RN - 0 (Receptor, Adenosine A2A) RN - 0 (Sulfonamides) RN - 0 (Triazoles) RN - 120225-54-9 (2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine) RN - 97161-97-2 (staurosporine aglycone) RN - E0399OZS9N (Cyclic AMP) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) RN - K72T3FS567 (Adenosine) RN - M876330O56 (N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide) SB - IM MH - Adenosine/analogs & derivatives/pharmacology/*physiology MH - Adenosine A2 Receptor Agonists MH - Adenosine A2 Receptor Antagonists MH - Animals MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Carbazoles/pharmacology MH - Cyclic AMP/physiology MH - Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors MH - Data Interpretation, Statistical MH - Excitatory Postsynaptic Potentials/drug effects MH - Hippocampus/drug effects/physiology MH - In Vitro Techniques MH - Indole Alkaloids/pharmacology MH - Isoquinolines/pharmacology MH - Long-Term Potentiation/*drug effects MH - Male MH - Neuroprotective Agents/pharmacology MH - Phenethylamines/pharmacology MH - Phosphorylation/drug effects MH - Pyrimidines/pharmacology MH - Rats MH - Rats, Wistar MH - Receptor, Adenosine A2A/*physiology MH - Sulfonamides/pharmacology MH - Triazoles/pharmacology EDAT- 2008/04/04 09:00 MHDA- 2008/07/23 09:00 CRDT- 2008/04/04 09:00 PHST- 2007/10/23 00:00 [received] PHST- 2008/01/08 00:00 [revised] PHST- 2008/01/30 00:00 [accepted] PHST- 2008/04/04 09:00 [pubmed] PHST- 2008/07/23 09:00 [medline] PHST- 2008/04/04 09:00 [entrez] AID - S0028-3908(08)00038-5 [pii] AID - 10.1016/j.neuropharm.2008.01.011 [doi] PST - ppublish SO - Neuropharmacology. 2008 May;54(6):924-33. doi: 10.1016/j.neuropharm.2008.01.011. Epub 2008 Feb 8.