PMID- 11050179
OWN - NLM
STAT- MEDLINE
DCOM- 20010111
LR  - 20181113
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 97
IP  - 23
DP  - 2000 Nov 7
TI  - Endogenous regulators of G protein signaling proteins regulate presynaptic 
      inhibition at rat hippocampal synapses.
PG  - 12810-5
AB  - Presynaptic inhibition mediated by G protein-coupled receptors (GPCRs) can 
      develop and decay in a few seconds. This time course is too rapid to be accounted 
      for by the intrinsic GTPase activity of Galpha subunits alone. Here, we test the 
      hypothesis that endogenous regulators of G protein signaling (RGS proteins) are 
      required for rapid, brief presynaptic inhibition. Endogenous G protein alpha 
      subunits were uncoupled from GPCRs by treating cultures with pertussis toxin 
      (PTX). Adenoviral expression of mutant PTX-insensitive (PTX-i) Galpha(i1-3) or 
      Galpha(o) subunits rescued adenosine-induced presynaptic inhibition in cultured 
      hippocampal neurons. Expression of double mutant Galpha(i1) or Galpha(o) subunits 
      that were both PTX-insensitive and unable to bind RGS proteins (PTX/RGS-i) also 
      rescued presynaptic inhibition. Presynaptic inhibition mediated by PTX/RGS-i 
      subunits decayed much more slowly after agonist removal than that mediated by 
      PTX-i subunits or native G proteins. The onset of presynaptic inhibition mediated 
      by PTX/RGS-i Galpha(o) was also slower than that mediated by PTX-i Galpha(o). In 
      contrast, the onset of presynaptic inhibition mediated by PTX/RGS-i Galpha(i1) 
      was similar to that mediated by PTX-i Galpha(i1). These results suggest that 
      endogenous RGS proteins regulate the time course of G protein signaling in 
      mammalian central nervous system presynaptic terminals.
FAU - Chen, H
AU  - Chen H
AD  - Department of Pharmacology and Toxicology, Medical College of Georgia, and 
      Medical Research Service, Veterans Affairs Medical Center, Augusta, GA 30912, 
      USA.
FAU - Lambert, N A
AU  - Lambert NA
LA  - eng
GR  - R01 NS036455/NS/NINDS NIH HHS/United States
GR  - R29 NS036455/NS/NINDS NIH HHS/United States
GR  - NS36455/NS/NINDS NIH HHS/United States
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  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (GTP-Binding Protein Regulators)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Virulence Factors, Bordetella)
RN  - EC 2.4.2.31 (Pertussis Toxin)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gi-Go)
RN  - EC 3.6.5.1 (Heterotrimeric GTP-Binding Proteins)
SB  - IM
MH  - Adenoviridae
MH  - Animals
MH  - Cells, Cultured
MH  - GTP-Binding Protein Regulators/genetics/*metabolism
MH  - GTP-Binding Protein alpha Subunits, Gi-Go/genetics/*metabolism
MH  - Gene Expression
MH  - Genetic Vectors
MH  - Heterotrimeric GTP-Binding Proteins/genetics/*metabolism
MH  - Hippocampus/cytology
MH  - Neural Inhibition
MH  - Neurons/cytology/*physiology
MH  - Pertussis Toxin
MH  - Presynaptic Terminals/*physiology
MH  - Rats
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Signal Transduction/*physiology
MH  - Synaptic Transmission/*physiology
MH  - Virulence Factors, Bordetella/genetics/metabolism
PMC - PMC18846
EDAT- 2000/10/26 11:00
MHDA- 2001/02/28 10:01
PMCR- 2001/05/07
CRDT- 2000/10/26 11:00
PHST- 2000/10/26 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/10/26 11:00 [entrez]
PHST- 2001/05/07 00:00 [pmc-release]
AID - 230260397 [pii]
AID - 2603 [pii]
AID - 10.1073/pnas.230260397 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12810-5. doi: 10.1073/pnas.230260397.