Effects of subchronic lithium chloride treatment on G-protein subunits (Golf, Ggamma7) and adenylyl cyclase expressed specifically in the rat striatum.
Lithium salt has been widely used as a treatment for mania, but the mechanism of its effect remains unknown. Previously, by studying c-fos expression, we showed that the striatum was a possible target region for the antimanic effects of lithium salt. The present study focused on the effect of subchronic lithium chloride treatment on G-proteins (Golf, Ggamma7) and adenylyl cyclase type V, which are expressed specifically in the rat striatum. Subchronic lithium chloride treatment significantly increased the level of Golf protein, a stimulant alpha-subunit of G-protein, by 53.5% (P<0.01), but the levels of Ggamma7 and adenylyl cyclase type V did not change. This increased level of Golf protein was found after 2 weeks of lithium chloride treatment, but not after 1 week, and the level returned to the basal level 1 week after withdrawal of lithium chloride. This result suggests that the level of Golf protein increases to compensate for the suppression of the adenylyl cyclase system by lithium, and that this increase may account for the "rebound" phenomenon, which is the relapse observed after abrupt discontinuation of lithium salt treatment.
Miki
M
M
Department of Neuropsychiatry, Graduate School of Medicine and Dentistry, Okayama University, 2-5-1 Shikata-cho, 700-8558, Okayama, Japan.
Hamamura
T
T
Ujike
H
H
Lee
Y
Y
Habara
T
T
Kodama
M
M
Ohashi
K
K
Tanabe
Y
Y
Kuroda
S
S
D000262:Adenylyl Cyclases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D044385:GTP-Binding Protein alpha Subunits; D019204:GTP-Binding Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D020962:Heterotrimeric GTP-Binding Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D008094:Lithium / Q000097:blood; D018021:Lithium Chloride / Q000008:administration & dosage*; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D044385:GTP-Binding Protein alpha Subunits; D012333:RNA, Messenger; C084618:olfactory G protein subunit alpha olf; D008094:Lithium; D019204:GTP-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins; D000262:Adenylyl Cyclases; D018021:Lithium Chloride