Fluoxetine modulates G protein alpha s, alpha q, and alpha 12 subunit mRNA expression in rat brain.
Signal-transducing G proteins are central to the coordination of receptor-effector communication. We have explored the effects of long-term fluoxetine administration of G alpha s, G alpha i1, G alpha i2, G alpha o, G alpha q and G alpha 12 mRNA expression in various rat brain regions using reverse transcriptase-polymerase chain reaction (RT-PCR)-mediated cross-species partial cDNA cloning. Northern blot analysis, and RNase protection assay techniques. Fluoxetine decreased G alpha s mRNA in midbrain, while mRNA expression of the novel G protein alpha subunits, G alpha q and G alpha 12, was increased in neostriatum and frontal cortex. We conclude that in addition to post-translational modification, regulation of G protein function by antidepressant drugs may occur at the level of gene expression.
Lesch
K P
KP
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20892.
Hough
C J
CJ
Aulakh
C S
CS
Wolozin
B L
BL
Tolliver
T J
TJ
Hill
J L
JL
Akiyoshi
J
J
Chuang
D M
DM
Murphy
D L
DL
D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D005473:Fluoxetine / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D015870:Gene Expression; D008297:Male; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012260:Ribonucleases / Q000378:metabolism
D012333:RNA, Messenger; D005473:Fluoxetine; D012260:Ribonucleases; D019204:GTP-Binding Proteins