PMID- 16890252
OWN - NLM
STAT- MEDLINE
DCOM- 20070302
LR  - 20141120
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 52
IP  - 1
DP  - 2007 Jan
TI  - GABAA receptor-associated phosphoinositide 3-kinase is required for 
      insulin-induced recruitment of postsynaptic GABAA receptors.
PG  - 146-55
AB  - Type A gamma-aminobutyric acid (GABAA) receptors mediate most of the fast 
      inhibitory synaptic transmission within the vertebrate brain. The regulation of 
      this inhibition is vital in modulating neural activity. One regulator of GABAA 
      receptor function is insulin, which can serve to enhance GABAA receptor-mediated 
      miniature inhibitory postsynaptic currents, via an increase in the number of 
      receptors at the plasma membrane. We set out to investigate the molecular 
      mechanisms involved in the insulin-induced potentiation of GABAA 
      receptor-mediated responses, by examining the role of phosphoinositide 3-kinase 
      (PI3-K), a key mediator of the insulin response within the brain. We found that 
      PI3-K associates with the GABAA receptor, and this interaction is increased 
      following insulin treatment. Additionally, the beta2 subunit of the GABAA 
      receptor appears to mediate the insulin-stimulated association with the 
      N-terminal SH2 domain of the p85 subunit of PI3-K. Our results imply a mechanism 
      whereby insulin can regulate changes in synaptic transmission through its 
      downstream actions on the GABAA receptor.
FAU - Vetiska, S M
AU  - Vetiska SM
AD  - Programme in Brain and Behavior Research, Hospital for Sick Children and 
      Department of Laboratory Medicine and Pathobiology, University of Toronto, 
      Toronto, Canada.
FAU - Ahmadian, G
AU  - Ahmadian G
FAU - Ju, W
AU  - Ju W
FAU - Liu, L
AU  - Liu L
FAU - Wymann, M P
AU  - Wymann MP
FAU - Wang, Y T
AU  - Wang YT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060804
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Insulin)
RN  - 0 (Protein Subunits)
RN  - 0 (Receptors, GABA-A)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Cells, Cultured
MH  - Drug Interactions
MH  - Embryo, Mammalian
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression Regulation/*drug effects
MH  - Hippocampus/cytology
MH  - Immunoprecipitation/methods
MH  - In Vitro Techniques
MH  - Inhibitory Postsynaptic Potentials/drug effects/physiology/radiation effects
MH  - Insulin/*pharmacology
MH  - Male
MH  - Models, Molecular
MH  - Neurons/*drug effects
MH  - Patch-Clamp Techniques/methods
MH  - Phosphatidylinositol 3-Kinases/*physiology
MH  - Protein Subunits/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Rats, Wistar
MH  - Receptors, GABA-A/*metabolism
MH  - Synaptic Transmission/*drug effects/physiology
EDAT- 2006/08/08 09:00
MHDA- 2007/03/03 09:00
CRDT- 2006/08/08 09:00
PHST- 2006/06/01 00:00 [received]
PHST- 2006/06/25 00:00 [revised]
PHST- 2006/06/26 00:00 [accepted]
PHST- 2006/08/08 09:00 [pubmed]
PHST- 2007/03/03 09:00 [medline]
PHST- 2006/08/08 09:00 [entrez]
AID - S0028-3908(06)00200-0 [pii]
AID - 10.1016/j.neuropharm.2006.06.023 [doi]
PST - ppublish
SO  - Neuropharmacology. 2007 Jan;52(1):146-55. doi: 10.1016/j.neuropharm.2006.06.023. 
      Epub 2006 Aug 4.