EurekaMag.com logo
+ Site Statistics
References:
53,869,633
Abstracts:
29,686,251
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

RANTES modulates the release of glutamate in human neocortex



RANTES modulates the release of glutamate in human neocortex



Journal of Neuroscience 28(47): 12231-12240



The effects of the recombinant chemokine human RANTES (hRANTES) on the release of glutamate from human neocortex glutamatergic nerve endings were investigated. hRANTES facilitated the spontaneous release of d [(3)H]D-aspartate ([(3)H]DASP-) by binding Pertussis toxin-sensitive G-protein-coupled receptors (GPCRs), whose activation caused Ca(2+) mobilization from inositol trisphosphate-sensitive stores and cytosolic tyrosine kinase-mediated phosphorylations. Facilitation of release switched to inhibition when the effects of hRANTES on the 12 mM K(+)-evoked [(3)H]D-ASP exocytosis were studied. Inhibition of exocytosis relied on activation of Pertussis toxin-sensitive GPCRs negatively coupled to adenylyl cyclase. Both hRANTES effects were prevented by met-RANTES, an antagonist at the chemokine receptors (CCRs) of the CCR1, CCR3, and CCR5 subtypes. Interestingly, human neocortex glutamatergic nerve endings seem to possess all three receptor subtypes. Blockade of CCR1 and CCR5 by antibodies against the extracellular domain of CCRs prevented both the hRANTES effect on [(3)H]D-ASP release, whereas blockade of CCR3 prevented inhibition, but not facilitation, of release. The effects of RANTES on the spontaneous and the evoked release of [(3)H]D-ASP were also observed in experiments with mouse cortical synaptosomes, which may therefore represent an appropriate animal model to study RANTES-induced effects on neurotransmission. It is concluded that glutamate transmission can be modulated in opposite directions by RANTES acting at distinct CCR receptor subtypes coupled to different transduction pathways, consistent with the multiple and sometimes contrasting effects of the chemokine.

(PDF emailed within 0-6 h: $19.90)

Accession: 055333239

Download citation: RISBibTeXText

PMID: 19020017

DOI: 10.1523/JNEUROSCI.3212-08.2008



Related references

Human eosinophils express RANTES mRNA and store and release biologically active RANTES protein. Journal of Allergy & Clinical Immunology 97(1 PART 3): 243, 1996

Human eosinophils express messenger RNA encoding RANTES and store and release biologically active RANTES protein. European Journal of Immunology 26(1): 70-76, 1996

Metabotropic glutamate receptor modulates high threshold calcium current of neurons acutely isolated from rat neocortex. Society for Neuroscience Abstracts 17(1-2): 956, 1991

Cranial afferent glutamate heterosynaptically modulates GABA release onto second-order neurons via distinctly segregated metabotropic glutamate receptors. Journal of Neuroscience 24(42): 9332-9340, 2004

Adenosine modulates depolarization-induced release of 3H-noradrenaline from slices of rat brain neocortex. European Journal of Pharmacology 49(3): 305-308, 1978

Agonists of group III metabotropic glutamate receptors reduce the synthesis and release of the CCR chemokine RANTES in cultured astrocytes. Society for Neuroscience Abstracts 26(1-2): Abstract No -606 24, 2000

Human herpesvirus-6 modulates RANTES production in primary human endothelial cell cultures. Journal of Medical Virology 70(3): 451-458, 2003

The effect of glutamate receptor blockers on glutamate release following spinal cord injury. Lack of evidence for an ongoing feedback cascade of damage -> glutamate release -> damage -> glutamate release -> etc. Brain Research 1038(1): 92-99, 2005

The effect of glutamate receptor blockers on glutamate release following spinal cord injury. Lack of evidence for an ongoing feedback cascade of damage --> glutamate release --> damage --> glutamate release --> etc. Brain Research 1038(1): 92-99, 2005

Dendritic release of glutamate suppresses synaptic inhibition of pyramidal neurons in rat neocortex. Journal of Physiology (Cambridge) 528(3): 489-496, November 1st, 2000

Inhibition of K+-induced increase in synaptosomal i and K+-evoked glutamate release from slices of rat neocortex by gabapentin. Society for Neuroscience Abstracts 25(1-2): 2254, 1999

Release of acetylcholine, gamma-aminobutyrate, dopamine and glutamate, and activity of some related enzymes, in rat gustatory neocortex. Brain Research 523(1): 100-104, 1990

Glutamate release from human glioma cells is a consequence of mislocalization of sodium-dependent glutamate transporter and upregulation of cystine-glutamate exchange. Society for Neuroscience Abstracts 25(1-2): 432, 1999

RANTES modulates TLR4-induced cytokine secretion in human peripheral blood monocytes. Journal of Immunology 177(8): 5077-5087, 2006

Glutamate modulates spinal cord norepinephrine release. Society for Neuroscience Abstracts 21(1-3): 1108, 1995