PMID- 16150057
OWN - NLM
STAT- MEDLINE
DCOM- 20060120
LR  - 20220309
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 95
IP  - 4
DP  - 2005 Nov
TI  - Constitutive expression of CCR2 chemokine receptor and inhibition by MCP-1/CCL2 
      of GABA-induced currents in spinal cord neurones.
PG  - 1023-34
AB  - In the CNS, immune-like competent cells (microglia and astrocytes) were first 
      described as potential sites of chemokine synthesis, but more recent evidence has 
      indicated that neurones might also express chemokines and their receptors. The 
      aim of the present work was to investigate further, both in vivo and in vitro, CC 
      Chemokine Family Receptor 2 (CCR2) expression and functionality in rat spinal 
      cord neurones. First, we demonstrated by RT-PCR and western blot analysis that 
      CCR2 mRNA and protein were present in spinal extracts. Furthermore, we showed by 
      immunolabelling that CCR2 was exclusively expressed by neurones in spinal 
      sections of healthy rat. Finally, to test the functionality of CCR2, we used 
      primary cultures of rat spinal neurones. In this model, similar to what was 
      observed in vivo, CCR2 mRNA and protein were expressed by neurones. Cultured 
      neurones stimulated with Monocyte Chemoattractant Protein-1 (MCP-1)/CCL2, the 
      best characterized CCR2 agonist, showed activation of the Akt pathway. Finally, 
      patch-clamp recording of cultured spinal neurones was used to investigate whether 
      MCP-1/CCL2 could modulate their electrophysiological properties. MCP-1 alone did 
      not affect the electrical properties of spinal neurones, but potently and 
      efficiently inhibited GABA(A)-mediated GABAergic responses in these neurones. 
      These data constitute the first demonstration of a modulatory role of MCP-1 on 
      GABAergic neurotransmission and contribute to our understanding of the roles of 
      CCR2 and MCP-1/CCL2 in spinal cord physiology, in particular with respect to 
      nociceptive transmission, as well as the implication of this chemokine in 
      neuronal adaptation or dysfunction during neuropathy.
FAU - Gosselin, Romain Daniel
AU  - Gosselin RD
AD  - INSERM U732-UPMC, Hopital Saint-Antoine, Paris, France.
FAU - Varela, Carolina
AU  - Varela C
FAU - Banisadr, G
AU  - Banisadr G
FAU - Mechighel, Patricia
AU  - Mechighel P
FAU - Rostene, William
AU  - Rostene W
FAU - Kitabgi, Patrick
AU  - Kitabgi P
FAU - Melik-Parsadaniantz, Stephane
AU  - Melik-Parsadaniantz S
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050907
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Ccr2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (ELAV Proteins)
RN  - 0 (GABA Antagonists)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
RN  - Y37615DVKC (Bicuculline)
SB  - IM
MH  - Animals
MH  - Autoradiography/methods
MH  - Bicuculline/pharmacology
MH  - Blotting, Northern/methods
MH  - Blotting, Western/methods
MH  - Cells, Cultured
MH  - Chemokine CCL2/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - ELAV Proteins/metabolism
MH  - Embryo, Mammalian
MH  - Female
MH  - GABA Antagonists/pharmacology
MH  - Gene Expression Regulation/*drug effects/physiology
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Immunohistochemistry/methods
MH  - Male
MH  - Membrane Potentials/drug effects/physiology
MH  - Neurons/*drug effects/physiology
MH  - Oncogene Protein v-akt/metabolism
MH  - Patch-Clamp Techniques/methods
MH  - Phosphorylation
MH  - Pregnancy
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/genetics/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
MH  - Spinal Cord/*cytology
MH  - gamma-Aminobutyric Acid/*pharmacology
EDAT- 2005/09/10 09:00
MHDA- 2006/01/21 09:00
CRDT- 2005/09/10 09:00
PHST- 2005/09/10 09:00 [pubmed]
PHST- 2006/01/21 09:00 [medline]
PHST- 2005/09/10 09:00 [entrez]
AID - JNC3431 [pii]
AID - 10.1111/j.1471-4159.2005.03431.x [doi]
PST - ppublish
SO  - J Neurochem. 2005 Nov;95(4):1023-34. doi: 10.1111/j.1471-4159.2005.03431.x. Epub 
      2005 Sep 7.