Pharmacological and phosphoproteomic approaches to roles of protein kinase C in kappa opioid receptor-mediated effects in mice

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Pharmacological and phosphoproteomic approaches to roles of protein kinase C in kappa opioid receptor-mediated effects in mice. / Liu, Jeffrey J; Chiu, Yi-Ting; Chen, Chongguang; Huang, Peng; Mann, Matthias; Liu-Chen, Lee-Yuan.

I: Neuropharmacology, Bind 181, 15.12.2020, s. 108324.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Liu, JJ, Chiu, Y-T, Chen, C, Huang, P, Mann, M & Liu-Chen, L-Y 2020, 'Pharmacological and phosphoproteomic approaches to roles of protein kinase C in kappa opioid receptor-mediated effects in mice', Neuropharmacology, bind 181, s. 108324. https://doi.org/10.1016/j.neuropharm.2020.108324

APA

Liu, J. J., Chiu, Y-T., Chen, C., Huang, P., Mann, M., & Liu-Chen, L-Y. (2020). Pharmacological and phosphoproteomic approaches to roles of protein kinase C in kappa opioid receptor-mediated effects in mice. Neuropharmacology, 181, 108324. https://doi.org/10.1016/j.neuropharm.2020.108324

Vancouver

Liu JJ, Chiu Y-T, Chen C, Huang P, Mann M, Liu-Chen L-Y. Pharmacological and phosphoproteomic approaches to roles of protein kinase C in kappa opioid receptor-mediated effects in mice. Neuropharmacology. 2020 dec. 15;181:108324. https://doi.org/10.1016/j.neuropharm.2020.108324

Author

Liu, Jeffrey J ; Chiu, Yi-Ting ; Chen, Chongguang ; Huang, Peng ; Mann, Matthias ; Liu-Chen, Lee-Yuan. / Pharmacological and phosphoproteomic approaches to roles of protein kinase C in kappa opioid receptor-mediated effects in mice. I: Neuropharmacology. 2020 ; Bind 181. s. 108324.

Bibtex

@article{d07d6b240ad3419cb61bf1258e48e84f,

title = "Pharmacological and phosphoproteomic approaches to roles of protein kinase C in kappa opioid receptor-mediated effects in mice",

abstract = "Kappa opioid receptor (KOR) agonists possess adverse dysphoric and psychotomimetic effects, thus limiting their applications as non-addictive anti-pruritic and analgesic agents. Here, we showed that protein kinase C (PKC) inhibition preserved the beneficial antinociceptive and antipruritic effects of KOR agonists, but attenuated the adverse condition placed aversion (CPA), sedation, and motor incoordination in mice. Using a large-scale mass spectrometry-based phosphoproteomics of KOR-mediated signaling in the mouse brain, we observed PKC-dependent modulation of G protein-coupled receptor kinases and Wnt pathways at 5 min; stress signaling, cytoskeleton, mTOR signaling and receptor phosphorylation, including cannabinoid receptor CB1 at 30 min. We further demonstrated that inhibition of CB1 attenuated KOR-mediated CPA. Our results demonstrated the feasibility of in vivo biochemical dissection of signaling pathways that lead to side effects.",

author = "Liu, {Jeffrey J} and Yi-Ting Chiu and Chongguang Chen and Peng Huang and Matthias Mann and Lee-Yuan Liu-Chen",

year = "2020",

month = dec,

day = "15",

doi = "10.1016/j.neuropharm.2020.108324",

language = "English",

volume = "181",

pages = "108324",

journal = "Neuropharmacology",

issn = "0028-3908",

publisher = "Pergamon Press",

}

RIS

TY - JOUR

T1 - Pharmacological and phosphoproteomic approaches to roles of protein kinase C in kappa opioid receptor-mediated effects in mice

AU - Liu, Jeffrey J

AU - Chiu, Yi-Ting

AU - Chen, Chongguang

AU - Huang, Peng

AU - Mann, Matthias

AU - Liu-Chen, Lee-Yuan

PY - 2020/12/15

Y1 - 2020/12/15

N2 - Kappa opioid receptor (KOR) agonists possess adverse dysphoric and psychotomimetic effects, thus limiting their applications as non-addictive anti-pruritic and analgesic agents. Here, we showed that protein kinase C (PKC) inhibition preserved the beneficial antinociceptive and antipruritic effects of KOR agonists, but attenuated the adverse condition placed aversion (CPA), sedation, and motor incoordination in mice. Using a large-scale mass spectrometry-based phosphoproteomics of KOR-mediated signaling in the mouse brain, we observed PKC-dependent modulation of G protein-coupled receptor kinases and Wnt pathways at 5 min; stress signaling, cytoskeleton, mTOR signaling and receptor phosphorylation, including cannabinoid receptor CB1 at 30 min. We further demonstrated that inhibition of CB1 attenuated KOR-mediated CPA. Our results demonstrated the feasibility of in vivo biochemical dissection of signaling pathways that lead to side effects.

AB - Kappa opioid receptor (KOR) agonists possess adverse dysphoric and psychotomimetic effects, thus limiting their applications as non-addictive anti-pruritic and analgesic agents. Here, we showed that protein kinase C (PKC) inhibition preserved the beneficial antinociceptive and antipruritic effects of KOR agonists, but attenuated the adverse condition placed aversion (CPA), sedation, and motor incoordination in mice. Using a large-scale mass spectrometry-based phosphoproteomics of KOR-mediated signaling in the mouse brain, we observed PKC-dependent modulation of G protein-coupled receptor kinases and Wnt pathways at 5 min; stress signaling, cytoskeleton, mTOR signaling and receptor phosphorylation, including cannabinoid receptor CB1 at 30 min. We further demonstrated that inhibition of CB1 attenuated KOR-mediated CPA. Our results demonstrated the feasibility of in vivo biochemical dissection of signaling pathways that lead to side effects.

U2 - 10.1016/j.neuropharm.2020.108324

DO - 10.1016/j.neuropharm.2020.108324

M3 - Journal article

C2 - 32976891

VL - 181

SP - 108324

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

ER -

ID: 259833055