5-HT1B Receptors: A Novel Target for Lithium Possible Involvement in Mood Disorders

Massot, O.

doi:10.1016/s0893-133x(99)00042-1

Cited by 54 publications

(33 citation statements)

References 44 publications

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“…It is interesting to note that several earlier studies reported that lithium selectively inhibited 5-HT binding to 5-HT1BR, reduced 5-HT1BR-induced GTP␥s binding, and abolished 5-HT1BR-reduced adenylyl cyclase activity (Massot et al, 1999). Similar results were observed in human platelets from both healthy and depressed subjects where lithium dose-dependently reversed the inhibitory effect of a 5-HT1BR agonist on adenylyl cyclase (Januel et al, 2002).…”

supporting

confidence: 76%

“…It is interesting that several early investigations observed that lithium had a noticeable effect on 5-HT1BR (Massot et al, 1999), but the mechanism of this action was not revealed. In this study, we used several experimental approaches to determine whether GSK3 has an impact in agonist-induced activation of 5-HT1Rs and whether subtypes of 5-HT1Rs are differentially regulated by GSK3.…”

mentioning

confidence: 99%

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Regulation of Serotonin 1B Receptor by Glycogen Synthase Kinase-3

Chen

Salinas²,

Li³

2009

Mol Pharmacol

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In response to 5-hydroxytryptamine (5-HT), the type 1 serotonin receptors (5-HT1Rs) preferentially couple to the inhibitory G protein and elicit many physiological and behavioral processes. However, their regulation by intracellular protein kinases has not been fully investigated. In this study, we identified that glycogen synthase kinase-3 (GSK3) differentially regulates 5-HT1Rs. In receptor-expressing cells and brain slices, activation of both 5-HT1AR and 5-HT1BR reduced forskolin-stimulated cAMP production, but only the effect of 5-HT1BR was abolished by selective GSK3 inhibitors, deletion of GSK3␤ by RNAi, or overexpression of impaired GSK3␤ mutants (R96A and K85,86A). A consensus GSK3 phosphorylation sequence was identified between the serine-154 and threonine-158 in the second intracellular loop of 5-HT1BR. Mutation of either serine-154 or threonine-158 to alanine significantly reduced response of 5-HT1BR to 5-HT. Active GSK3␤ interacted with resting 5-HT1BR to form a protein complex. The interaction was enhanced by receptor activation, abolished by GSK3 inhibitors, and dependent on the phosphorylation state of serine-154. In addition, regulation of 5-HT1BR by GSK3 changed the dynamics of agonist-induced cell surface receptor internalization, in which lack of phosphorylation at Ser154 resulted in sustained reduction of 5-HT1BR at the cell surface. Although the physiological consequences of selective regulation of 5-HT1BR by GSK3 remain to be identified, findings in this study reveal a new function of GSK3 as a protein kinase that is able to selectively regulate G protein-coupled receptors.Most serotonin (5-HT) receptors are G protein-coupled receptors (GPCRs) that are classified by their sequence homology and by the type of G proteins and signal transduction pathways with which they are associated (Hannon and Hoyer, 2008). The type 1 5-HT receptors (5-HT1Rs), including subtypes A (5-HT1AR) and B (5-HT1BR), are mainly coupled to the inhibitory G protein, which links the receptors to inhibition of adenylyl cyclase and regulation of several other signal pathways (Raymond et al., 2001). 5-HT1AR and 5-HT1BR are found in several brain areas, such as the dorsal raphe nucleus, nucleus accumbens, cerebral cortex, hippocampus, and striatum. In the raphe nucleus, 5-HT1AR and 5-HT1BR are characterized as autoreceptors, with the former located at the somatodendritic area and the latter at the axon terminus. In many other brain regions and peripheral tissues, 5-HT1AR and 5-HT1BR also function as heteroreceptors in nonserotonergic neurons (Hannon and Hoyer, 2008). 5-HT1Rs are involved in many physiological processes in the brain, especially regulating turnover of 5-HT and other neurotransmitters in several brain regions (Ase et al., 2000). 5-HT1Rs are a major group of serotonin receptors that modulate behaviors, especially those relevant to neuropsychiatric diseases, such as anxiety, mood, and aggression (Gingrich and Hen, 2001). Therefore, proper regulation of activities of 5-HT1Rs is crucially important in main...

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supporting

confidence: 76%

mentioning

confidence: 99%

Regulation of Serotonin 1B Receptor by Glycogen Synthase Kinase-3

Chen

Salinas²,

Li³

2009

Mol Pharmacol

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“…Chronic lithium is reported to increase the 5-HT concentration in the serotonergic synaptic cleft by reducing 5-HT 1 density, particularly the density of presynaptic 5-HT 1B receptors, but it does not appear to affect 5-HT 2A/ 2C receptor density (Friedman and Wang, 1988;Goodwin, 1989;Haddjeri et al, 2000;Januel et al, 2002;Massot et al, 1999;Mizuta and Segawa, 1988;Redrobe and Bourin, 1999). As 5-HT 1B receptors depress presynaptic 5-HT release, lithium's elevation of k* for AA in auditory and visual areas may result from derepressed 5-HT release, elevated 5-HT in the cleft, or an increased 5-HT 2A/2C -mediated activation of PLA 2 (Januel et al, 2002;Redrobe and Bourin, 1999).…”

Section: Discussionmentioning

confidence: 99%

Chronic Lithium Administration to Rats Selectively Modifies 5-HT2A/2C Receptor-Mediated Brain Signaling Via Arachidonic Acid

Basselin

Chang

Seemann

et al. 2004

Neuropsychopharmacol

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The effects of chronic lithium administration on regional brain incorporation coefficients k* of arachidonic acid (AA), a marker of phospholipase A 2 (PLA 2 ) activation, were determined in unanesthetized rats administered i.p. saline or 1 mg/kg i.p. (7)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), a 5-HT 2A/2C receptor agonist. After injecting [1-14 C]AA intravenously, k* (brain radioactivity/integrated plasma radioactivity) was measured in each of 94 brain regions by quantitative autoradiography. Studies were performed in rats fed a LiCl or a control diet for 6 weeks. In the control diet rats, DOI significantly increased k* in widespread brain areas containing 5-HT 2A/2C receptors. In the LiCl-fed rats, the significant positive k* response to DOI did not differ from that in control diet rats in most brain regions, except in auditory and visual areas, where the response was absent. LiCl did not change the head turning response to DOI seen in control rats. In summary, LiCl feeding blocked PLA 2 -mediated signal involving AA in response to DOI in visual and auditory regions, but not generally elsewhere. These selective effects may be related to lithium's therapeutic efficacy in patients with bipolar disorder, particularly its ability to ameliorate hallucinations in that disease.

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“…The increase in nuclear charge per unit volume indicated that nuclear strength of Li + ions in treated lithium powder probably increased after biofield treatment. It is reported that Li + plays an important role in central nervous system in releasing the serotonin from neurons [5,27,28]. Thus, it is assumed that serotonin releasing activity of Li + in treated sample may be higher as compared to control.…”

Section: Thermogravimetric Analysis-differential Thermal Analysis (Tgmentioning

confidence: 99%

“…In addition, it is widely spread in central nervous system and interacts with many neurotransmitters and receptors, thus increasing serotonin synthesis [4]. Further, it is also reported that lithium ions (Li + ) can increase the release of serotonin or 5-hydroxy tryptamine by neurons in the brain [5]. Furthermore, the most commonly prescribed lithium salts include lithium carbonate (Li 2 CO 3 ), lithium orotate (C 5 H 3 LiN 2 O 4 ), and lithium citrate (Li 3 C 6 H 5 O 7 ) for pharmacological treatment in mentally disordered patients [6,7].…”

Section: Introductionmentioning

confidence: 99%

Physical, Atomic and Thermal Properties of Biofield Treated Lithium Powder

2015

J Adv Chem Eng

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5-HT1B Receptors: A Novel Target for Lithium Possible Involvement in Mood Disorders

Cited by 54 publications

References 44 publications

Regulation of Serotonin 1B Receptor by Glycogen Synthase Kinase-3

Regulation of Serotonin 1B Receptor by Glycogen Synthase Kinase-3

Chronic Lithium Administration to Rats Selectively Modifies 5-HT2A/2C Receptor-Mediated Brain Signaling Via Arachidonic Acid

Physical, Atomic and Thermal Properties of Biofield Treated Lithium Powder

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