Identification of addicsin/GTRAP3-18 as a chronic morphine-augmented gene in amygdala.
Using subtractive cloning, we identified a 1.4 kb mRNA that was ubiquitously expressed in various tissues; this mRNA was highly up-regulated in amygdala nuclei in mice when morphine was repeatedly administered but not when an opiate-receptor antagonist was co-administered. The mRNA encodes a 23 kDa protein, designated 'addicsin'. This contains two putative PKC-phosphorylation motifs and several hydrophobic regions, and was recovered in a soluble protein fraction of brain lysate. Its primary structure showed 98% identity with that of rat glutamate-transporter-associated protein 3-18 (GTRAP3-18), a putative modulator of neural glutamate-transporter EAAC1. Up-regulation of addicsin expression by morphine may affect glutamate uptake in the amygdala, causing mice to develop morphine tolerance and dependence.
Ikemoto
Mitsushi J
MJ
Gene Discovery Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan. m.ikemoto@aist.go.jp
Inoue
Koutarou
K
Akiduki
Saori
S
Osugi
Takeshi
T
Imamura
Toru
T
Ishida
Norio
N
Ohtomi
Michiko
M
D000595:Amino Acid Sequence; D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002352:Carrier Proteins / Q000302:isolation & purification* / Q000378:metabolism*; D002490:Central Nervous System; D018076:DNA, Complementary; D006360:Heat-Shock Proteins; D017403:In Situ Hybridization; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009020:Morphine / Q000494:pharmacology*; D009292:Narcotic Antagonists; D009294:Narcotics / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000302:isolation & purification* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D015854:Up-Regulation
C464502:Arl6ip5 protein, mouse; D002352:Carrier Proteins; D018076:DNA, Complementary; D006360:Heat-Shock Proteins; D026901:Membrane Transport Proteins; D009292:Narcotic Antagonists; D009294:Narcotics; D012333:RNA, Messenger; D009020:Morphine; D011493:Protein Kinase C