Imipramine, but not lithium, induces the serine/threonine phosphatase activity of calcineurin without affecting its mRNA expression in the rat brain.
The influence of imipramine and lithium on the expression of calcineurin (CaN) and its serine/threonine phosphatase activity in the rat frontal cortex and hippocampus was examined. Northern blot analysis demonstrated that single or repeated (14 day) administration of imipramine did not affect the levels of CaN A (catalytic subunit) mRNA in rat brain. Similarly, the administration of lithium for 1 or 14 days had no effect on the expression of CaN A mRNA. In contrast, the acute administration of imipramine significantly increased CaN activity in the cortex and hippocampus. In addition, the chronic (14 day) administration also significantly increased CaN activity. However, administration of lithium for either 1 or 14 days did not influence CaN activity. These findings indicate that imipramine, but not lithium, increases the phosphatase activity of CaN, suggesting that the changes in neuronal functions induced by CaN may be involved in the molecular activity of imipramine.
Tanaka
Kazuhide
K
Department of Psychiatry, Shiga University of Medical Science, Otsu, Japan.
Takahashi
Jun
J
Morinobu
Shigeru
S
Fujimaki
Koichiro
K
Tsuji
Seiichi
S
Kato
Kunio
K
Ohkawa
Masako
M
Yamawaki
Shigeto
S
Kato
Nobumasa
N
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D019703:Calcineurin / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology*; D008094:Lithium / Q000494:pharmacology; D008297:Male; D010749:Phosphoprotein Phosphatases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D018759:Adrenergic Uptake Inhibitors; D012333:RNA, Messenger; D008094:Lithium; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D007099:Imipramine