Regulation of the glutamate transporter EAAC1 by expression and activation of delta-opioid receptor.
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 delta-opioid receptor (DOR) co-expressed with EAAC1 in Xenopus oocytes, but not the micro-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.
Xia
Peng
P
Max-Planck Guest Laboratory at the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, CAS, 320 Yue Yang Road, Shanghai 200031, China.
Pei
Gang
G
Schwarz
Wolfgang
W
D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D027341:Excitatory Amino Acid Transporter 1 / Q000096:biosynthesis / Q000502:physiology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000378:metabolism; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000096:biosynthesis / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism; D014982:Xenopus laevis
D027341:Excitatory Amino Acid Transporter 1; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D018698:Glutamic Acid; D020881:Enkephalin, D-Penicillamine (2,5)-