PMID- 16242118
OWN - NLM
STAT- MEDLINE
DCOM- 20051230
LR  - 20131121
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 70
IP  - 12
DP  - 2005 Dec 5
TI  - Excitatory amino acid transporters expressed by synovial fibroblasts in rats with 
      collagen-induced arthritis.
PG  - 1744-55
AB  - Although previous studies have demonstrated increased levels of the brain 
      neurotransmitter glutamate (Glu) in the synovial fluid from patients with 
      arthritis, not much attention has been paid to the possible role of Glu in joint 
      synovial tissues to date. Constitutive expression of mRNA was for the first time 
      shown with glutamate aspartate transporter, glutamate transporter-1 and 
      excitatory amino acid carrier-1 (EAAC1), in addition to with particular 
      ionotropic and metabotropic Glu receptors, in cultured synovial fibroblasts 
      prepared from knee joints of male Lewis rats. Immunohistochemical analysis 
      revealed high localization of immunoreactive EAAC1 at synovial tissues. The 
      accumulation of [3H]Glu occurred in a temperature- and sodium-dependent manner in 
      cultured synovial fibroblasts, with a Km of 23.1+/-1.1 microM and a Vmax of 
      237.1+/-31.1 pmol/(mg protein min), respectively. In rats with arthritis induced 
      by immunization to type-II collagen, marked increases were seen in hind paw 
      volume, cytokine mRNA expression and Glu levels in synovial tissues, in addition 
      to histological erosion. In cultured synovial fibroblasts prepared from these 
      arthritic rats, [3H]Glu accumulation was drastically increased with biochemical 
      and pharmacological profiles similar to those seen in normal synovial 
      fibroblasts. The exposure to Glu at 500 microM doubled the incorporation of 
      5-bromo-2'-deoxyuridine in cultured synovial fibroblasts of arthritic but not 
      normal rats, without significantly affecting mRNA expression of different 
      cytokines in both synovial fibroblasts. These results suggest that Glu may at 
      least in part play a role in mechanisms associated with cellular proliferation 
      through particular transporters functionally expressed by synovium in rheumatoid 
      arthritis.
FAU - Hinoi, Eiichi
AU  - Hinoi E
AD  - Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, 
      Kanazawa University Graduate School of Natural Science and Technology, Kanazawa, 
      Ishikawa 920-1192, Japan.
FAU - Ohashi, Ryosuke
AU  - Ohashi R
FAU - Miyata, Susumu
AU  - Miyata S
FAU - Kato, Yasuko
AU  - Kato Y
FAU - Iemata, Mika
AU  - Iemata M
FAU - Hojo, Hironori
AU  - Hojo H
FAU - Takarada, Takeshi
AU  - Takarada T
FAU - Yoneda, Yukio
AU  - Yoneda Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20051019
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Cytokines)
RN  - 0 (Excitatory Amino Acid Transporter 1)
RN  - 0 (Excitatory Amino Acid Transporter 2)
RN  - 0 (Excitatory Amino Acid Transporter 3)
RN  - 0 (RNA, Messenger)
RN  - 0 (Slc1a1 protein, rat)
RN  - 3KX376GY7L (Glutamic Acid)
SB  - IM
MH  - Animals
MH  - Arthritis, Experimental/*metabolism
MH  - Cells, Cultured
MH  - Cytokines/biosynthesis
MH  - Excitatory Amino Acid Transporter 1/genetics
MH  - Excitatory Amino Acid Transporter 2/*genetics
MH  - Excitatory Amino Acid Transporter 3/*genetics
MH  - Fibroblasts/metabolism
MH  - Glutamic Acid/*metabolism/pharmacology
MH  - Male
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Signal Transduction
MH  - Synovial Membrane/cytology/*metabolism
EDAT- 2005/10/26 09:00
MHDA- 2005/12/31 09:00
CRDT- 2005/10/26 09:00
PHST- 2005/05/31 00:00 [received]
PHST- 2005/09/13 00:00 [revised]
PHST- 2005/09/15 00:00 [accepted]
PHST- 2005/10/26 09:00 [pubmed]
PHST- 2005/12/31 09:00 [medline]
PHST- 2005/10/26 09:00 [entrez]
AID - S0006-2952(05)00600-3 [pii]
AID - 10.1016/j.bcp.2005.09.010 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2005 Dec 5;70(12):1744-55. doi: 10.1016/j.bcp.2005.09.010. 
      Epub 2005 Oct 19.