Crucial Interactions Between Selective Serotonin Uptake Inhibitors and Sigma-1 Receptor in Heart Failure

Bhuiyan, Md. Shenuarin; Tagashira, Hideaki; Fukunaga, Kohji

doi:10.1254/jphs.12r13cp

Cited by 29 publications

(21 citation statements)

References 40 publications

(69 reference statements)

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“…Extensive evidence has established that NE play major role in left ventricular hypertrophy and heart failure [58]. Therapy with selective serotonin reuptake inhibitors (SSRIs) is strongly recommended to reduce cardiovascular disease-induced morbidity and mortality [59]. However, the relationship between the NE, GC and 5-HT effect on myocardial injury have not been elucidated.…”

Section: Discussionmentioning

confidence: 99%

A Neuroendocrine Mechanism of Co-Morbidity of Depression-Like Behavior and Myocardial Injury in Rats

Wang

Liu²,

Wu³

et al. 2014

PLoS ONE

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Depression is generally a recurrent psychiatric disorder. Evidence shows that depression and cardiovascular diseases are common comorbid conditions, but the specific pathological mechanisms remain unclear. The purpose of this study is to determine the effects of depression induced by chronic unpredictable mild stress (CUMS) on myocardial injury and to further elucidate the biological mechanism of depression. Rats were used as a model. The CUMS procedure lasted for a total of 8 weeks. After 4 weeks of CUMS, treated rats exhibited a reduced sucrose preference and changes in scores on an open field test, body weight and content of 5-HT in the brain as compared with the values of these variables in controls. These changes indicated depression-like changes in CUMS rats and demonstrated the feasibility of the depression model. In addition, pathological changes in the myocardium and increased cardiomyocyte apoptosis demonstrated that myocardial injury had occurred after 6 weeks of CUMS and had increased significantly by the end of 8 weeks of CUMS. Plasma serotonin (5-HT), norepinephrine (NE) and epinephrine (E), all depression-related neuroendocrine factors, were measured by HPLC-ECD techniques, and the content of plasma corticosterone (GC) was evaluated by an I125–cortisol radioactivity immunoassay in control and CUMS rats. The results indicated that 5-HT had decreased, whereas NE, E and GC had increased in CUMS rats, and these factors might be associated with depression-induced myocardial injury. The effects of 5-HT, NE and GC on the survival rate of cultured cardiomyocytes were determined using an orthogonal design. The results showed that 5-HT was a more important factor affecting cell survival than GC or NE. The results suggested that normal blood levels of 5-HT had a cytoprotective effect. The neuroendocrine disorders characterized by decreased 5-HT combined with increased GC and NE mediated the occurrence of depression-induced myocardial injury.

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Section: Discussionmentioning

confidence: 99%

A Neuroendocrine Mechanism of Co-Morbidity of Depression-Like Behavior and Myocardial Injury in Rats

Wang

Liu²,

Wu³

et al. 2014

PLoS ONE

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“…This modulation could represent a secondary target involved in the effects of σR ligands on both the Glu and the 5-HT systems, thus leading to one primary target ( 377 , 828 ). Recently, practical treatment efforts have shown that σ1Rs are also one of the major pharmacological therapeutic targets of selective serotonin reuptake inhibitors [SSRIs] ( 829 ).…”

Section: Known σRs – Location and Effectsmentioning

confidence: 99%

Sigma receptors [σRs]: biology in normal and diseased states

Rousseaux

Greene

2015

Journal of Receptors and Signal Transduction

124

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This review compares the biological and physiological function of Sigma receptors [σRs] and their potential therapeutic roles. Sigma receptors are widespread in the central nervous system and across multiple peripheral tissues. σRs consist of sigma receptor one (σ1R) and sigma receptor two (σ2R) and are expressed in numerous regions of the brain. The sigma receptor was originally proposed as a subtype of opioid receptors and was suggested to contribute to the delusions and psychoses induced by benzomorphans such as SKF-10047 and pentazocine. Later studies confirmed that σRs are non-opioid receptors (not an µ opioid receptor) and play a more diverse role in intracellular signaling, apoptosis and metabolic regulation. σ1Rs are intracellular receptors acting as chaperone proteins that modulate Ca2+ signaling through the IP3 receptor. They dynamically translocate inside cells, hence are transmembrane proteins. The σ1R receptor, at the mitochondrial-associated endoplasmic reticulum membrane, is responsible for mitochondrial metabolic regulation and promotes mitochondrial energy depletion and apoptosis. Studies have demonstrated that they play a role as a modulator of ion channels (K+ channels; N-methyl-d-aspartate receptors [NMDAR]; inositol 1,3,5 triphosphate receptors) and regulate lipid transport and metabolism, neuritogenesis, cellular differentiation and myelination in the brain. σ1R modulation of Ca2+ release, modulation of cardiac myocyte contractility and may have links to G-proteins. It has been proposed that σ1Rs are intracellular signal transduction amplifiers. This review of the literature examines the mechanism of action of the σRs, their interaction with neurotransmitters, pharmacology, location and adverse effects mediated through them.

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“…For instance, sigma-1 receptor agonist SA4503 reduces cardiac hypertrophy and myocardial dysfunction by restoring mitochondrial Ca (2+) mobilization and ATP production in heart failure [163,164]. Antagonists could be detrimental to those in cardiac failure.…”

Section: Potential Barriers To Sigma Of-1 Receptor Antagonist Developmentioning

confidence: 99%

Sigma-1 receptors and animal studies centered on pain and analgesia

Davis

2015

Expert Opinion on Drug Discovery

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Sigma-1 receptor antagonists have a great potential as analgesics for acute neuropathic injury (herpes zoster, acute postoperative pain and chemotherapy induced neuropathy) and may, as an additional benefit, prevent the development of chronic neuropathic pain. Antagonists are potentially effective as adjuvants to opioid therapy when used early to prevent analgesic tolerance. Drug development is complicated by the complexity of sigma-1 receptor pharmacodynamics and its multiple targets, the lack of a specific sigma-1 receptor antagonist, and potential side effects due to on-target toxicities (cognitive impairment, depression).

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Crucial Interactions Between Selective Serotonin Uptake Inhibitors and Sigma-1 Receptor in Heart Failure

Cited by 29 publications

References 40 publications

A Neuroendocrine Mechanism of Co-Morbidity of Depression-Like Behavior and Myocardial Injury in Rats

A Neuroendocrine Mechanism of Co-Morbidity of Depression-Like Behavior and Myocardial Injury in Rats

Sigma receptors [σRs]: biology in normal and diseased states

Sigma-1 receptors and animal studies centered on pain and analgesia

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