title: RANTES-mediated control of excitatory amino acid release in mouse spinal cord.
abstract: The impact of Regulated upon Activation Normal T cells Expressed and Secreted (RANTES) on the release of pre-loaded [³H]D-aspartate ([³H]D-ASP) from mouse spinal cord synaptosomes was investigated. RANTES (0.01-1 nM) failed to affect the spontaneous release, but facilitated the 15 mM K⁺-evoked overflow of [³H]D-ASP. Incubation of synaptosomes with antibodies raised against the chemokine receptor (CCR)1 and CCR5 proteins prevented RANTES-induced facilitation of glutamate exocytosis, whereas anti-CCR3 antibody was inefficacious. Accordingly, BX513 and D-Ala-peptide T-amide (DAPTA) CCR1 and CCR5 antagonists, respectively, prevented RANTES-induced effect, whereas the CCR3 antagonist SB 328437 was inactive. To compare these findings to previous results, we quantified the effects of CCR antagonists on the RANTES-induced modifications of the spontaneous and the K⁺-evoked [³H]D-ASP release in the mouse cortex. Here, CCR1 and CCR5, but not CCR3, antagonists prevented the RANTES-mediated [³H]D-ASP release, whereas RANTES-induced inhibition of the 12 mM K⁺-evoked [³H]D-ASP exocytosis was also antagonized by SB 328437. Facilitation of glutamate exocytosis in spinal cord relied on PLC-dependent mobilization of Ca²⁺ from IP₃-sensitive stores; adenylyl cyclase was not involved. CCR1, CCR3 and CCR5 receptor proteins were present in spinal cord synaptosomal and gliosomal lysates, although RANTES-induced changes to glutamate release could not be observed in gliosomes. Our results confirm the role of RANTES as modulator of glutamate transmission.
authors.affiliation: Department of Experimental Medicine, Pharmacology and Toxicology Section, University of Genoa, Genoa, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Di Prisco
authors.forename: Maria
authors.initials: M
authors.lastname: Summa
authors.forename: Vineetha
authors.initials: V
authors.lastname: Chellakudam
authors.forename: Pia Irene Anna
authors.initials: PI
authors.lastname: Rossi
authors.forename: Anna
authors.initials: A
authors.lastname: Pittaluga
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018925:Chemokines / Q000378:metabolism; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D018846:Excitatory Amino Acids / Q000378:metabolism*; D005089:Exocytosis / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D018946:Chemokine CCL5; D018925:Chemokines; D018846:Excitatory Amino Acids; D019707:Receptors, Chemokine; D001224:Aspartic Acid; D018698:Glutamic Acid; D002118:Calcium