Effect of lithium in vitro and after chronic treatment on human platelet adenylate cyclase activity: Postreceptor modification of second messenger signal amplification

Ebstein, Richard P.; Moscovich, Daniel G.; Zeevi, Shulamit; Amiri, Zamir; Lerer, Bernard

doi:10.1016/0165-1781(87)90026-6

Cited by 31 publications

(16 citation statements)

References 20 publications

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“…At therapeutic concentrations, lithium is known to inhibit a phosphodiesterase family of enzymes, which includes fructose 1,6-biphosphatase (FBPase), bisphosphate nucleotidase (BPNase), inositol monophosphatase (IMPase), and inositol polyphosphate 1-phosphatase (IPPase) all sharing a common sequence motif (York et al, 1995; Spiegelberg et al, 1999; Gould, 2006). Competition with magnesium for binding sites also modulates actions of lithium on G-protein-mediated cellular signaling transduction pathways (GTP binding and cyclic AMP production) through inhibition of adenylyl cyclase (Ebstein et al, 1976; Ebstein et al, 1978; Andersen and Geisler, 1984; Ebstein et al, 1987; Newman and Belmaker, 1987; Avissar et al, 1988; Mørk and Geisler, 1989; Minadeo et al, 2001; Srinivasan et al, 2004). Lithium selectively inhibits specific isoforms of adenylyl cyclase that are associated with antidepressant-like behaviors in animal models (Mann et al, 2008; Mann et al, 2009).…”

Section: Lithium and Magnesiummentioning

confidence: 99%

Molecular actions and clinical pharmacogenetics of lithium therapy

Can

Schulze

Gould

2014

Pharmacology Biochemistry and Behavior

100

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Mood disorders, including bipolar disorder and depression, are relatively common human diseases for which pharmacological treatment options are often not optimal. Among existing pharmacological agents and mood stabilizers used for the treatment of mood disorders, lithium has a unique clinical profile. Lithium has efficacy in the treatment of bipolar disorder generally, and in particular mania, while also being useful in the adjunct treatment of refractory depression. In addition to antimanic and adjunct antidepressant efficacy, lithium is also proven effective in the reduction of suicide and suicidal behaviors. However, only a subset of patients manifests beneficial responses to lithium therapy and the underlying genetic factors of response are not exactly known. Here we discuss preclinical research suggesting mechanisms likely to underlie lithium’s therapeutic actions including direct targets inositol monophosphatase and glycogen synthase kinase-3 (GSK-3) among others, as well as indirect actions including modulation of neurotrophic and neurotransmitter systems and circadian function. We follow with a discussion of current knowledge related to the pharmacogenetic underpinnings of effective lithium therapy in patients within this context. Progress in elucidation of genetic factors that may be involved in human response to lithium pharmacology has been slow, and there is still limited conclusive evidence for the role of a particular genetic factor. However, the development of new approaches such as genome-wide association studies (GWAS), and increased use of genetic testing and improved identification of mood disorder patients sub-groups will lead to improved elucidation of relevant genetic factors in the future.

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Section: Lithium and Magnesiummentioning

confidence: 99%

Molecular actions and clinical pharmacogenetics of lithium therapy

Can

Schulze

Gould

2014

Pharmacology Biochemistry and Behavior

100

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“…In a number of cell types, including platelets and striatal membranes, recent evidence suggests that PKC may enhance basal A.C. activity by attenuating the tonic inhibitory influence of Gi; this may also represent a mechanism by which chronic lithium administration alters both basal and post-receptor mediated A.C. activity in human platelets Risby et al, 1991) and rat cortex Masana et al, 1992). Additionally, several laboratories have now demonstrated that chronic lithium treatment attenuates both receptor-mediated adenylyl cyclase activity and phosphoinositide turnover in rodents and in man (Casebolt and Jope, 1989;Chuang, 1989;Ebstein et al, 1980Ebstein et al, , 1987Ebstein et al, , 1988Godfrey et al, 1989a;Kendall and Nahorski, 1987;Mork and Geisler et al, 1989;Newman et al, 1983Newman et al, , 1987Song and Jope, 1992). Since PKC activation can affect both these transmembrane signaling pathways, PKC isozymes represent a reasonable target for an action of chronic lithium in modulating receptor-mediated second messenger systems in brain.…”

Section: Introductionmentioning

confidence: 99%

Long‐term action of lithium: A role for transcriptional and posttranscriptional factors regulated by protein kinase C

Manji

Lenox

1994

Synapse

119

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Lithium, a simple monovalent cation, represents one of psychiatry's most important treatments and is the most effective treatment for reducing both the frequency and severity of recurrent affective episodes. Despite extensive research, the underlying biologic basis for the therapeutic efficacy this drug remains unknown, and in recent years, research has focused on signal transduction pathways to explain lithium's efficacy in treating both poles of manic-depressive illness. Critical to attributions of therapeutic relevance to any observed biochemical effect, however, is the observation that the characteristic prophylactic action of lithium in stabilizing the profound mood cycling of bipolar disorder requires a lag period for onset and is not immediately reversed upon discontinuation of treatment. Biochemical changes requiring such prolonged administration of a drug suggest alterations at the genomic level but, until recently, little has been known about the transcriptional and posttranscriptional factors regulated by chronic drug treatment, although long-term changes in neuronal synaptic function are known to be dependent upon the selective regulation of gene expression. In this paper, we will present evidence to show that chronic lithium exerts significant transcriptional and posttranscriptional effects, and that these actions of lithium may be mediated via protein kinase C (PKC)-induced alterations in nuclear transcription regulatory factors responsible for modulating the expression of proteins involved in long-term neural plasticity and cellular response. Such target sites for chronic lithium may help unravel the processes by which a simple monovalent cation can produce a long-term stabilization of mood in individuals vulnerable to bipolar illness.

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“…The other major receptor coupled second messenger system upon which lithium exerts significant effects is the cyclic AMP generating system. Forn and Valdecasas were the first to report that lithium in vitro attenuated noradrenaline stimulated cyclic AMP accumulation [72]; since then numerous studies have clearly demonstrated that cyclic AMP accumulation by various neurotransmitters and hormones is inhibited by lithium at therapeutic concentrations both in vivo and in vitro [12,38,73–87]. Noradrenaline and adenosine stimulated cyclic adenosine monophosphate (cAMP) accumulation in rat cortical slices is inhibited significantly by 1–2 mmol/L lithium, although whether this can be generalised to human brain tissue has not yet been fully determined [88].…”

Section: Adenylate Cyclasementioning

confidence: 99%

“…Noradrenaline and adenosine stimulated cyclic adenosine monophosphate (cAMP) accumulation in rat cortical slices is inhibited significantly by 1–2 mmol/L lithium, although whether this can be generalised to human brain tissue has not yet been fully determined [88]. Studies in humans have demonstrated that lithium treatment at therapeutic levels results in an attenuation of the plasma cAMP increase in response to adrenaline [89–91] as well as evidence for an attenuation of receptor coupling to adenylate cyclase (AC) in peripheral cells [38,77,80,81,92,93]. In fact, lithium inhibition of vasopressin‐sensitive or thyroid‐stimulating hormone sensitive AC is generally believed to underlie two of lithium's more common side‐effects, namely nephrogenic diabetes insipidus and hypothyroidism [94–97].…”

Section: Adenylate Cyclasementioning

confidence: 99%

Signalling pathways in the brain: Cellular transduction of mood stabilisation in the treatment of manic-depressive illness

Manji

McNamara²,

Chen³

et al. 1999

Aust N Z J Psychiatry

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The long-term treatment of manic-depressive illness (MDI) likely involves the strategic regulation of signalling pathways and gene expression in critical neuronal circuits. Accumulated evidence has identified signalling pathways, in particular the family of protein kinase C (PKC) isozymes, as targets for the long-term action of lithium. Chronic lithium administration produces a reduction in the expression of PKC alpha and epsilon, as well as a major PKC substrate, MARCKS, which has been implicated in long-term neuroplastic events in the developing and adult brain. More recently, studies have demonstrated robust effects of lithium on another kinase system, GSK-3beta, and on neuroprotective/neurotrophic proteins in the brain. Given the key roles of these signalling cascades in the amplification and integration of signals in the central nervous system, these findings have clear implications not only for research into the neurobiology of MDI, but also for the future development of novel and innovative treatment strategies.

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Effect of lithium in vitro and after chronic treatment on human platelet adenylate cyclase activity: Postreceptor modification of second messenger signal amplification

Cited by 31 publications

References 20 publications

Molecular actions and clinical pharmacogenetics of lithium therapy

Molecular actions and clinical pharmacogenetics of lithium therapy

Long‐term action of lithium: A role for transcriptional and posttranscriptional factors regulated by protein kinase C

Signalling pathways in the brain: Cellular transduction of mood stabilisation in the treatment of manic-depressive illness

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