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Regulation of the glutamate transporter EAAC1 by expression and activation of δ‐opioid receptor
Author(s) -
Xia Peng,
Pei Gang,
Schwarz Wolfgang
Publication year - 2006
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2006.04897.x
Subject(s) - glutamatergic , glutamate receptor , opioid , microbiology and biotechnology , excitatory postsynaptic potential , inhibitory postsynaptic potential , neuroscience , chemistry , transporter , hippocampal formation , opioid receptor , biology , receptor , biochemistry , gene
Glutamate transporters play an essential role in regulating temporal and spatial glutamate concentration in the synaptic cleft. The excitatory amino acid carrier 1 (EAAC1) is a neuronal‐specific transporter. Opioid receptors are found to modulate the glutamatergic system in brain, but the regulatory mechanism remains to be investigated. Here we report that the δ‐opioid receptor (DOR) co‐expressed with EAAC1 in Xenopus oocytes, but not the µ‐opioid receptor, down‐regulates EAAC1 function, and that [ d ‐Pen 2,5 ]‐enkephalin stimulation of DOR can counteract the down‐regulation of the EAAC1‐mediated uptake. Results from co‐immunoprecipitation and immunofluorescence microscopy in both oocytes and rat hippocampal neurons indicate co‐localization and suggest direct interaction between DOR and EAAC1. The results suggest that DOR can reduce EAAC1 function by direct protein–protein interaction and that activation of DOR releases the inhibitory interaction. We suggest that this mechanism may be important for modulation of the glutamatergic system following opioid stimulation.