PMID- 18495895 OWN - NLM STAT- MEDLINE DCOM- 20080626 LR - 20211020 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 28 IP - 21 DP - 2008 May 21 TI - Postsynaptic action of brain-derived neurotrophic factor attenuates alpha7 nicotinic acetylcholine receptor-mediated responses in hippocampal interneurons. PG - 5611-8 LID - 10.1523/JNEUROSCI.5378-07.2008 [doi] AB - Nicotinic mechanisms acting on the hippocampus influence attention, learning, and memory and constitute a significant therapeutic target for many neurodegenerative, neurological, and psychiatric disorders. Here, we report that brain-derived neurotrophic factor (BDNF) (1-100 ng/ml), a member of the neurotrophin gene family, rapidly decreases alpha7 nicotinic acetylcholine receptor responses in interneurons of the hippocampal CA1 stratum radiatum. Such effect is dependent on the activation of the TrkB receptor and involves the actin cytoskeleton; noteworthy, it is compromised when the extracellular levels of the endogenous neuromodulator adenosine are reduced with adenosine deaminase (1 U/ml) or when adenosine A(2A) receptors are blocked with SCH 58261 (2-(2-furanyl)-7-(2-phenylethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine) (100 nm). The intracellular application of U73122 (1-[6[[(17beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione) (5 mum), a broad-spectrum inhibitor of phospholipase C, or GF 109203X (bisindolylmaleimide I) (2 mum), a general inhibitor of protein kinase C isoforms, blocks BDNF-induced inhibition of alpha7 nicotinic acetylcholine receptor function. Moreover, in conditions of simultaneous intracellular dialysis of the fast Ca(2+) chelator BAPTA (10 mm) and removal of extracellular Ca(2+) ions, the inhibitory action of BDNF is further prevented. The present findings disclose a novel target for rapid actions of BDNF that might play important roles on synaptic transmission and plasticity in the brain. FAU - Fernandes, Catarina C AU - Fernandes CC AD - Institute of Pharmacology and Neurosciences, Faculty of Medicine and Unit of Neurosciences, Institute of Molecular Medicine, University of Lisbon, 1649-028 Lisbon, Portugal. cfernandes@fm.ul.pt FAU - Pinto-Duarte, Antonio AU - Pinto-Duarte A FAU - Ribeiro, Joaquim Alexandre AU - Ribeiro JA FAU - Sebastiao, Ana M AU - Sebastiao AM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Bungarotoxins) RN - 0 (Chelating Agents) RN - 0 (Chrna7 protein, rat) RN - 0 (Excitatory Amino Acid Agonists) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Pyrimidines) RN - 0 (Receptors, Nicotinic) RN - 0 (Sodium Channel Blockers) RN - 0 (Triazoles) RN - 0 (alpha7 Nicotinic Acetylcholine Receptor) RN - 4368-28-9 (Tetrodotoxin) RN - 526U7A2651 (Egtazic Acid) RN - 6OTE87SCCW (6-Cyano-7-nitroquinoxaline-2,3-dione) RN - 76326-31-3 (2-amino-5-phosphopentanoic acid) RN - HG18B9YRS7 (Valine) RN - K22DDW77C0 (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid) RN - N9YNS0M02X (Acetylcholine) SB - IM MH - 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology MH - Acetylcholine/pharmacology MH - Analysis of Variance MH - Animals MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Bungarotoxins/pharmacology MH - Chelating Agents/pharmacology MH - Drug Interactions MH - Egtazic Acid/analogs & derivatives/pharmacology MH - Excitatory Amino Acid Agonists/pharmacology MH - Excitatory Postsynaptic Potentials/*drug effects/physiology MH - Hippocampus/*cytology MH - In Vitro Techniques MH - Interneurons/*drug effects/physiology MH - Male MH - Patch-Clamp Techniques/methods MH - Protein Kinase Inhibitors/pharmacology MH - Pyrimidines/pharmacology MH - Rats MH - Receptors, Nicotinic/*physiology MH - Sodium Channel Blockers/pharmacology MH - Tetrodotoxin/pharmacology MH - Triazoles/pharmacology MH - Valine/analogs & derivatives/pharmacology MH - alpha7 Nicotinic Acetylcholine Receptor PMC - PMC6670615 COIS- The authors declare no competing financial interests. EDAT- 2008/05/23 09:00 MHDA- 2008/06/27 09:00 PMCR- 2008/11/21 CRDT- 2008/05/23 09:00 PHST- 2008/05/23 09:00 [pubmed] PHST- 2008/06/27 09:00 [medline] PHST- 2008/05/23 09:00 [entrez] PHST- 2008/11/21 00:00 [pmc-release] AID - 28/21/5611 [pii] AID - 3355237 [pii] AID - 10.1523/JNEUROSCI.5378-07.2008 [doi] PST - ppublish SO - J Neurosci. 2008 May 21;28(21):5611-8. doi: 10.1523/JNEUROSCI.5378-07.2008.