Purinergic signaling: a potential therapeutic target for depression and chronic pain

Zou, Yuting; Yang, Runan; Li, Lin; Xu, Xiaoxiao; Liang, Shangdong

doi:10.1007/s11302-021-09801-x

Cited by 23 publications

(17 citation statements)

References 66 publications

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“…Although mice lacking high-affinity fluoxetine interactions with SERT also display losses in antidepressant activity ( 51 ), others have concluded that nonserotoninergic mechanisms drive antidepressant actions in humans ( 26 ), although counterarguments exist ( 27 ). Purinergic receptors are widely expressed in the nervous system and have been implicated in depression ( 52 – 54 ). Given the association between inflammation and depression and our findings of non–SERT-mediated fluoxetine activity, it is possible that fluoxetine may exert multiple effects, including antagonizing purinergic receptors.…”

Section: Discussionmentioning

confidence: 99%

Fluoxetine restrains allergic inflammation by targeting an FcɛRI-ATP positive feedback loop in mast cells

Haque,

Taruselli,

Kee

et al. 2023

Sci. Signal.

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There is a clinical need for new treatment options addressing allergic disease. Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressants that have anti-inflammatory properties. We tested the effects of the SSRI fluoxetine on IgE-induced function of mast cells, which are critical effectors of allergic inflammation. We showed that fluoxetine treatment of murine or human mast cells reduced IgE-mediated degranulation, cytokine production, and inflammatory lipid secretion, as well as signaling mediated by the mast cell activator ATP. In a mouse model of systemic anaphylaxis, fluoxetine reduced hypothermia and cytokine production. Fluoxetine was also effective in a model of allergic airway inflammation, where it reduced bronchial responsiveness and inflammation. These data show that fluoxetine suppresses mast cell activation by impeding an FcɛRI-ATP positive feedback loop and support the potential repurposing of this SSRI for use in allergic disease.

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Section: Discussionmentioning

confidence: 99%

Fluoxetine restrains allergic inflammation by targeting an FcɛRI-ATP positive feedback loop in mast cells

Haque,

Taruselli,

Kee

et al. 2023

Sci. Signal.

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“…pain-depression comorbidity. [114][115][116] In a medication overuse headache model, microglial P2X7R has been reported to contribute to NLRP3 inflammasome activation in the trigeminal nucleus caudalis. 117 Likewise, in rats with monosodium iodoacetate-induced joint damage, spinal microglial P2X7R was increased due to elevated ATP levels within the cerebral spinal fluid (CSF), impacting pain perception.…”

Section: Involvement Of P2x7r In Other Types Of Painmentioning

confidence: 99%

Involvement of microglial P2X7 receptor in pain modulation

Zhang,

Gao,

Zhang

et al. 2023

CNS Neurosci Ther

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BackgroundPain is a rapid response mechanism that compels organisms to retreat from the harmful stimuli and triggers a repair response. Nonetheless, when pain persists for extended periods, it can lead to adverse changes into in the individual’s brain, negatively impacting their emotional state and overall quality of life. Microglia, the resident immune cells in the central nervous system (CNS), play a pivotal role in regulating a variety of pain‐related disorders. Specifically, recent studies have shed light on the central role that microglial purinergic ligand‐gated ion channel 7 receptor (P2X7R) plays in regulating pain. In this respect, the P2X7R on microglial membranes represents a potential therapeutic target.AimsTo expound on the intricate link between microglial P2X7R and pain, offering insights into potential avenues for future research.MethodsWe reviewed 140 literature and summarized the important role of microglial P2X7R in regulating pain, including the structure and function of P2X7R, the relationship between P2X7R and microglial polarization, P2X7R‐related signaling pathways, and the effects of P2X7R antagonists on pain regulation.ResultsP2X7R activation is related to M1 polarization of microglia, while suppressing P2X7R can transfer microglia from M1 into M2 phenotype. And targeting the P2X7R‐mediated signaling pathways helps to explore new therapy for pain alleviation. P2X7R antagonists also hold potential for translational and clinical applications in pain management.ConclusionsMicroglial P2X7R holds promise as a potential novel pharmacological target for clinical treatments due to its distinctive structure, function, and the development of antagonists.

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“…The family of purinergic receptors mediates purinergic signaling, and these are divided into three classes: P 1 , P 2 X, and P 2 Y. P 1 and P 2 Y purinergic receptors are metabotropic G‐protein coupled receptors activated primarily by adenosine and ATP, respectively. The class of P 2 X receptors includes seven known members (P 2 X 1 through P 2 X 7 ) that are ligand‐gated ion channels activated by ATP to mediate excitatory signaling in post‐synaptic neurons (Zou et al, 2021). Furthermore, glial cells express a range of purinergic receptors and ATP has been shown to be a key mediator of neuron–glia and glia–glia signaling (Cotrina et al, 2000; Fields & Burnstock, 2006).…”

Section: Novel Targets and Radiotracersmentioning

confidence: 99%

Beyond monoamines: I. Novel targets and radiotracers for Positron emission tomography imaging in psychiatric disorders

Lopresti

Royse

Mathis

et al. 2022

Journal of Neurochemistry

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With the emergence of positron emission tomography (PET) in the late 1970s, psychiatry had access to a tool capable of non‐invasive assessment of human brain function. Early applications in psychiatry focused on identifying characteristic brain blood flow and metabolic derangements using radiotracers such as [15O]H2O and [18F]FDG. Despite the success of these techniques, it became apparent that more specific probes were needed to understand the neurochemical bases of psychiatric disorders. The first neurochemical PET imaging probes targeted sites of action of neuroleptic (dopamine D2 receptors) and psychoactive (serotonin receptors) drugs. Based on the centrality of monoamine dysfunction in psychiatric disorders and the measured success of monoamine‐enhancing drugs in treating them, the next 30 years witnessed the development of an armamentarium of PET radiopharmaceuticals and imaging methodologies for studying monoamines. Continued development of monoamine‐enhancing drugs over this time however was less successful, realizing only modest gains in efficacy and tolerability. As patent protection for many widely prescribed and profitable psychiatric drugs lapsed, drug development pipelines shifted away from monoamines in search of novel targets with the promises of improved efficacy, or abandoned altogether. Over this period, PET radiopharmaceutical development activities closely paralleled drug development priorities resulting in the development of new PET imaging agents for non‐monoamine targets. Part one of this review will briefly survey novel PET imaging targets with relevance to the field of psychiatry, which include the metabotropic glutamate receptor type 5 (mGluR5), purinergic P2X7 receptor, type 1 cannabinoid receptor (CB1), phosphodiesterase 10A (PDE10A), and describe radiotracers developed for these and other targets that have matured to human subject investigations. Current limitations of the targets and techniques will also be discussed.

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Purinergic signaling: a potential therapeutic target for depression and chronic pain

Cited by 23 publications

References 66 publications

Fluoxetine restrains allergic inflammation by targeting an FcɛRI-ATP positive feedback loop in mast cells

Fluoxetine restrains allergic inflammation by targeting an FcɛRI-ATP positive feedback loop in mast cells

Involvement of microglial P2X7 receptor in pain modulation

Beyond monoamines: I. Novel targets and radiotracers for Positron emission tomography imaging in psychiatric disorders

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