A COMPARISON OF LITHIUM EFFECTS ON HUMAN BRAIN AND RAT BRAIN NORADRENALINE‐SENSITIVE ADENYLATE CYCLASE
作者:
Ehud Klein,
R.H. Belmaker,
Michael Newman,
Jan Gruszkiewicz,
期刊:
Acta Pharmacologica et Toxicologica
(WILEY Available online 1985)
卷期:
Volume 56,
issue S1
页码: 15-20
ISSN:0001-6683
年代: 1985
DOI:10.1111/j.1600-0773.1985.tb02495.x
出版商: Blackwell Publishing Ltd
关键词: Lithium;cyclic AMP;cortex;human brain;noradrenaline
数据来源: WILEY
摘要:
Abstract:Lithium (Li) is a drug with numerous biochemical effects. Many of these biochemical effects occur only at high Li concentrations, or disappear after chronic Li treatment. Such effects are probably not related to Li's mechanism of therapeutic action. Inhibition of noradrenaline (NE)‐sensitive adenylate cyclase has been proposed as a possible therapeutic mechanism of action for Li. Tolerance does not develop to this effect, which has been reported to occur reliably beginning at 2mM Li in rat cortex. Since 2mM Li is at the upper limit of therapeutic levels in humans, controversy has continued as to whether Li inhibition of NE‐sensitive adenylate cyclase is a mechanism of Li's therapeutic action or a mechanism of Li toxicity. We hypothesized that human brain NE‐sensitive adenylate cyclase may be more sensitive to Li inhibition than rat brain NE‐sensitive adenylate cyclase. Fresh cortical human grey matter was obtained from the edges of surgically removed brain tumors in seven patients. Results showed significant inhibition of NE‐sensitive adenylate cyclase at 1mM Li. These results support the possibility that inhibition of NE‐sensitive adenylate cyclase is a mechanism of Li's therape
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