RANTES-mediated control of excitatory amino acid release in mouse spinal cord

Autor: Silvia Di Prisco, Anna Pittaluga, Vineetha Chellakudam, Maria Summa, Pia Irene Anna Rossi
Rok vydání: 2012
Předmět:
Zdroj: Journal of Neurochemistry. 121:428-437
ISSN: 0022-3042
DOI: 10.1111/j.1471-4159.2012.07720.x
Popis: J. Neurochem. (2012) 121, 428–437. 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.
Databáze: OpenAIRE
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