PMID- 8848010
OWN - NLM
STAT- MEDLINE
DCOM- 19961022
LR  - 20161123
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 48
IP  - 6
DP  - 1995 Dec
TI  - Platelet-derived growth factor receptor is a novel modulator of type A 
      gamma-aminobutyric acid-gated ion channels.
PG  - 1099-107
AB  - Platelet-derived growth factor (PDGF) and PDGF receptors (PDGFRs) are 
      ubiquitously expressed in the mammalian central nervous system, where they exert 
      trophic actions on both neuronal and glial cells. However, the acute actions of 
      PDGF on synaptic transmission are unknown. We report a novel regulatory action of 
      PDGF/PDGFR. Activation of PDGFRs inhibited the function of native type A 
      gamma-aminobutyric acid (GABAA) receptors (GABAA-RS) in rat hippocampal CA1 
      pyramidal neurons and mouse brain membrane vesicles. The mechanism of this 
      inhibition was studied with a panel of mutant PDGFRS-beta coexpressed with cloned 
      human GABAA-Rs in Xenopus oocytes. These experiments revealed that phospholipase 
      C-gamma is the protein that relays the inhibitory signal from PDGFRS to GABAA-Rs. 
      Experiments with microinjected EGTA and inositol-1, 3, 4-triphosphate 
      demonstrated that inhibition of GABAA-Rs depended on a phospholipase 
      C-gamma-mediated increase in intracellular Ca(2+)-levels. The PDGFR-induced 
      inhibitory effect was independent of the subunit composition of GABAA-RS. 
      Moreover, GABAA-RS composed of alpha 1 beta 1 S409A subunits, which do not 
      contain any known protein kinase C phosphorylation sites, were inhibited by PDGF 
      to the same extent as wild-type GABAA-RS. Inhibitors of protein kinase C, 
      CA2+/calmodulin-dependent protein kinase II, calcineurin, and tyrosine 
      phosphatases did not affect the modulatory actions of PDGFR. In conclusion, our 
      results suggest that PDGFRs exert potent modulatory actions on GABAA-R-dependent 
      inhibitory synaptic transmission. These regulatory actions of PDGF could play 
      important roles in the function of the mammalian central nervous system during 
      physiological and pathophysiological conditions.
FAU - Valenzuela, C F
AU  - Valenzuela CF
AD  - Department of Pharmacology, University of Colorado Health Sciences Center, Denver 
      80262, USA.
FAU - Kazlauskas, A
AU  - Kazlauskas A
FAU - Brozowski, S J
AU  - Brozowski SJ
FAU - Weiner, J L
AU  - Weiner JL
FAU - Demali, K A
AU  - Demali KA
FAU - McDonald, B J
AU  - McDonald BJ
FAU - Moss, S J
AU  - Moss SJ
FAU - Dunwiddie, T V
AU  - Dunwiddie TV
FAU - Harris, R A
AU  - Harris RA
LA  - eng
GR  - AA05399/AA/NIAAA NIH HHS/United States
GR  - AA07454/AA/NIAAA NIH HHS/United States
GR  - CA55063/CA/NCI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (GABA-A Receptor Antagonists)
RN  - 0 (Ion Channels)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - EC 2.7.10.1 (Receptors, Platelet-Derived Growth Factor)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Brain/physiology/ultrastructure
MH  - Calcium/physiology
MH  - Enzyme Inhibitors/pharmacology
MH  - GABA-A Receptor Antagonists
MH  - Hippocampus/physiology/ultrastructure
MH  - Ion Channel Gating/drug effects/*physiology
MH  - Ion Channels/drug effects/physiology
MH  - Macromolecular Substances
MH  - Male
MH  - Mice
MH  - Neurons/physiology/ultrastructure
MH  - Phosphoric Monoester Hydrolases/antagonists & inhibitors
MH  - Protein Kinase Inhibitors
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Platelet-Derived Growth Factor/*physiology
MH  - Xenopus
MH  - gamma-Aminobutyric Acid/pharmacology/*physiology
MH  - src Homology Domains/physiology
EDAT- 1995/12/01 00:00
MHDA- 1995/12/01 00:01
CRDT- 1995/12/01 00:00
PHST- 1995/12/01 00:00 [pubmed]
PHST- 1995/12/01 00:01 [medline]
PHST- 1995/12/01 00:00 [entrez]
PST - ppublish
SO  - Mol Pharmacol. 1995 Dec;48(6):1099-107.