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Lithium (medication)

About: Lithium (medication) is a research topic. Over the lifetime, 7880 publications have been published within this topic receiving 212698 citations. The topic is also known as: lithium salts & lithium.


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Journal ArticleDOI
TL;DR: It is shown that complete inhibition of IMPase has no effect on the morphogenesis of Xenopus embryos and a different hypothesis to explain the broad action of lithium is presented, which suggests that lithium acts through inhibition of glycogen synthase kinase-3 beta (GSK-3beta), which regulates cell fate determination in diverse organisms including Dictyostelium, Drosophila, and Xenopus.
Abstract: Lithium, one of the most effective drugs for the treatment of bipolar (manic-depressive) disorder, also has dramatic effects on morphogenesis in the early development of numerous organisms. How lithium exerts these diverse effects is unclear, but the favored hypothesis is that lithium acts through inhibition of inositol monophosphatase (IMPase). We show here that complete inhibition of IMPase has no effect on the morphogenesis of Xenopus embryos and present a different hypothesis to explain the broad action of lithium. Our results suggest that lithium acts through inhibition of glycogen synthase kinase-3 beta (GSK-3 beta), which regulates cell fate determination in diverse organisms including Dictyostelium, Drosophila, and Xenopus. Lithium potently inhibits GSK-3 beta activity (Ki = 2 mM), but is not a general inhibitor of other protein kinases. In support of this hypothesis, lithium treatment phenocopies loss of GSK-3 beta function in Xenopus and Dictyostelium. These observations help explain the effect of lithium on cell-fate determination and could provide insights into the pathogenesis and treatment of bipolar disorder.

2,372 citations

Journal ArticleDOI
TL;DR: The effects of cholinergic agonists and antagonists on the enzyme were examined and found none and the possibility that the inhibition of this enzyme by lithium ion is related to the pharmacological actions of lithium is discussed.

1,038 citations

Journal ArticleDOI
TL;DR: One of the pathways of sodium transport across the red-cell membrane, sodium-lithium countertransport, is faster in patients with essential hypertension than in control subjects, and this transport system accepts only sodium or lithium and is not inhibited by ouabain.
Abstract: This paper describes experiments showing that one of the pathways of sodium transport across the red-cell membrane, sodium–lithium countertransport, is faster in patients with essential hy...

853 citations

Journal ArticleDOI
TL;DR: The involvement of GSK-3 as an important mediator of DA and lithium action in vivo is supported and modulation of the Akt/GSK-3 pathway might be relevant to DA-related disorders, such as attention deficit hyperactivity disorder and schizophrenia.
Abstract: Dopamine (DA) is a neurotransmitter involved in the control of locomotion, emotion, cognition, and reward. Administration of lithium salts is known to inhibit DA-associated behaviors in experimental animal models through unknown mechanisms. Here, we used a pharmacogenetic approach to show that DA can exert its behavioral effects by acting on a lithium-sensitive signaling cascade involving Akt/PKB and glycogen synthase kinase 3 (GSK-3). In the mouse striatum, increased DA neurotransmission arising either from administration of amphetamine or from the lack of the DA transporter results in inactivation of Akt and concomitant activation of GSK-3α and GSK-3β. These biochemical changes are not affected by activation of the cAMP pathway but are effectively reversed either by inhibition of DA synthesis, D2 receptor blockade, or administration of lithium salts. Furthermore, pharmacological or genetic inhibition of GSK-3 significantly reduces DA-dependent locomotor behaviors. These data support the involvement of GSK-3 as an important mediator of DA and lithium action in vivo and suggest that modulation of the Akt/GSK-3 pathway might be relevant to DA-related disorders, such as attention deficit hyperactivity disorder and schizophrenia.

787 citations


Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20235,762
202211,369
2021368
2020178
2019166
2018128