TY - JOUR
T1 - Long-term lithium treatment selectively reduces receptor-coupled inositol phospholipid hydrolysis in rat brain
AU - Casebolt, Tamara L.
AU - Jope, Richard S.
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 1989/2/1
Y1 - 1989/2/1
N2 - Rats were treated with dietary lithium for 30 days, followed by assessment of the activity of the receptor-coupled inositol phospholipid second messenger-producing system in three brain regions. The major effect of long-term lithium treatment was a significant reduction of the response to norepinephrine in all three brain regions that were examined: the cerebral cortex, the hippocampus, and the striatum. After long-term lithium treatment, the response to serotonin was reduced in the hippocampus and striatum, but not the cortex, and the carbachol-induced response was only reduced in the striatum. Lithium treatment did not alter the incorporation of [3H] inositol into phospholipids, the in vitro lithium concentration-dependent accumulation of [3H]inositol monophosphate, or the stimulation by NaF of inositol phospholipid hydrolysis. These results indicate that the decreased responses to agonists after long-term lithium treatment are not likely to be due to depletion of inositol phospholipids or to altered activity of myo-inositol-1-phosphatase, phospholipase C, or the guanine nucleotide-binding protein. It is suggested that long-term lithium treatment may alter receptor number or receptor coupling, perhaps by phosphorylotion, thereby selectively lowering the agonist-induced generation of second messengers by the inositol phospholipid system.
AB - Rats were treated with dietary lithium for 30 days, followed by assessment of the activity of the receptor-coupled inositol phospholipid second messenger-producing system in three brain regions. The major effect of long-term lithium treatment was a significant reduction of the response to norepinephrine in all three brain regions that were examined: the cerebral cortex, the hippocampus, and the striatum. After long-term lithium treatment, the response to serotonin was reduced in the hippocampus and striatum, but not the cortex, and the carbachol-induced response was only reduced in the striatum. Lithium treatment did not alter the incorporation of [3H] inositol into phospholipids, the in vitro lithium concentration-dependent accumulation of [3H]inositol monophosphate, or the stimulation by NaF of inositol phospholipid hydrolysis. These results indicate that the decreased responses to agonists after long-term lithium treatment are not likely to be due to depletion of inositol phospholipids or to altered activity of myo-inositol-1-phosphatase, phospholipase C, or the guanine nucleotide-binding protein. It is suggested that long-term lithium treatment may alter receptor number or receptor coupling, perhaps by phosphorylotion, thereby selectively lowering the agonist-induced generation of second messengers by the inositol phospholipid system.
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U2 - 10.1016/0006-3223(89)90180-7
DO - 10.1016/0006-3223(89)90180-7
M3 - Article
C2 - 2536562
AN - SCOPUS:0024596206
VL - 25
SP - 329
EP - 340
JO - Biological Psychiatry
JF - Biological Psychiatry
SN - 0006-3223
IS - 3
ER -