PMID- 16443372 OWN - NLM STAT- MEDLINE DCOM- 20061122 LR - 20181201 IS - 1044-7431 (Print) IS - 1095-9327 (Electronic) IS - 1044-7431 (Linking) VI - 31 IP - 4 DP - 2006 Apr TI - Transforming growth factor alpha attenuates the functional expression of AMPA receptors in cortical GABAergic neurons. PG - 628-41 AB - In the developing neocortex, brain-derived neurotrophic factor (BDNF) exerts a trophic activity to increase the expression and channel activity of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor subunits. Here, we demonstrate that the epidermal growth factor (EGF) receptor (ErbB1) ligands exert the opposite biological activity in cultured neocortical neurons. Subchronic stimulation of ErbB1 with transforming growth factor alpha (TGFalpha), EGF, or heparin-binding EGF (HB-EGF) down-regulated protein expression of the GluR1 AMPA receptor subunit in cultured neocortical neurons. In agreement, TGFalpha treatment decreased the Bmax of [3H] AMPA binding and GluR1 mRNA levels. Immunocytochemistry revealed that the decrease in GluR1 was most pronounced in multipolar GABAergic neurons. To examine the physiological consequences, we recorded AMPA-evoked currents as well as miniature excitatory postsynaptic currents in morphologically identified putative GABAergic neurons in culture. Subchronic TGFalpha treatment decreased AMPA-triggered currents as well as the amplitude and frequency of miniature excitatory postsynaptic currents. An ErbB1 tyrosine kinase inhibitor, PD153035, inhibited the TGFalpha effect. Moreover, TGFalpha counteracted the neurotrophic activity of BDNF on AMPA receptor expression. Co-application of TGFalpha with BDNF blocked the BDNF-triggered up-regulation of AMPA receptor expression and currents. These observations reveal a negative regulatory activity of the ErbB1 ligand, TGFalpha, which reduces the input sensitivity of cortical GABAergic neurons to attenuate their inhibitory function. FAU - Namba, Hisaaki AU - Namba H AD - Department of Molecular Neurobiology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Niigata 951-8585, Japan. FAU - Nagano, Tadasato AU - Nagano T FAU - Iwakura, Yuriko AU - Iwakura Y FAU - Xiong, Huabao AU - Xiong H FAU - Jourdi, Hussam AU - Jourdi H FAU - Takei, Nobuyuki AU - Takei N FAU - Nawa, Hiroyuki AU - Nawa H LA - eng GR - P01 NS045260/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060126 PL - United States TA - Mol Cell Neurosci JT - Molecular and cellular neurosciences JID - 9100095 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Culture Media, Serum-Free) RN - 0 (Enzyme Inhibitors) RN - 0 (Hbegf protein, rat) RN - 0 (Heparin-binding EGF-like Growth Factor) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Ligands) RN - 0 (Protein Subunits) RN - 0 (Quinazolines) RN - 0 (Receptors, AMPA) RN - 0 (Transforming Growth Factor alpha) RN - 56-12-2 (gamma-Aminobutyric Acid) RN - 62229-50-9 (Epidermal Growth Factor) RN - 77521-29-0 (alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid) RN - EC 2.7.10.1 (ErbB Receptors) RN - TC62B68RSL (4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline) RN - TFZ3H25BS1 (glutamate receptor ionotropic, AMPA 1) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cells, Cultured MH - Cerebral Cortex/*cytology/metabolism MH - Culture Media, Serum-Free MH - Electrophysiology MH - Enzyme Inhibitors/pharmacology MH - Epidermal Growth Factor/metabolism MH - ErbB Receptors/antagonists & inhibitors/*metabolism MH - Heparin-binding EGF-like Growth Factor MH - Intercellular Signaling Peptides and Proteins MH - Ligands MH - Neurons/cytology/drug effects/*metabolism MH - Protein Subunits/metabolism MH - Quinazolines/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, AMPA/*metabolism MH - Transforming Growth Factor alpha/*metabolism/pharmacology MH - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/metabolism MH - gamma-Aminobutyric Acid/*metabolism PMC - PMC3683556 MID - NIHMS469080 EDAT- 2006/01/31 09:00 MHDA- 2006/12/09 09:00 PMCR- 2013/06/16 CRDT- 2006/01/31 09:00 PHST- 2005/08/08 00:00 [received] PHST- 2005/11/05 00:00 [revised] PHST- 2005/12/08 00:00 [accepted] PHST- 2006/01/31 09:00 [pubmed] PHST- 2006/12/09 09:00 [medline] PHST- 2006/01/31 09:00 [entrez] PHST- 2013/06/16 00:00 [pmc-release] AID - S1044-7431(05)00301-5 [pii] AID - 10.1016/j.mcn.2005.12.002 [doi] PST - ppublish SO - Mol Cell Neurosci. 2006 Apr;31(4):628-41. doi: 10.1016/j.mcn.2005.12.002. Epub 2006 Jan 26.