Regulation Of The Glutamate Transporter EAAC1 By Expression And Activation Of δ-opioid Receptor

Glutamate transporters play an essential role in regulating temporal and spatialglutamate concentration in synaptic cleft. The excitatory amino acid carrier 1(EAAC1), which is a neuronal specific transporter, regulates the synaptic glutamateconcentration. Opioid receptors are found to modulate the glutamatergic system inbrain, but the regulatory mechanism remains to be investigated. Here we report thatthe δ-opioid receptor (DOR) co-expressed with EAAC1 in Xenopus oocytes, but notthe μ-opioid receptor, down-regulates EAAC1 function, and that DPDPE stimulationof DOR can counteract the down regulation of the EAAC1-mediated uptake. Resultsfrom co-immunoprecipitation and immunofluorescence microscopy in both oocytesand rat hippocampal neurons indicate co-localization and suggest direct interactionbetween DOR and EAAC1, and this interaction reduce after DOR receptoractivation.Our results suggest that the delta opioid receptor can modulate EAAC1function by direct protein-protein interaction and that activation of DOR releases theinhibitory interaction. We suggest that this mechanism may be important formodulation of the glutamatergic system after opioid stimulation.