Molecular Interaction Between Butorphanol and κ-Opioid Receptor

Ji, Jiafu; Lin, Wen-Zhen; Vrudhula, Amey; Jin, Xi; Yeliseev, Alexei; Grothusen, John R.; Bu, Weiming; Liu, Renyu

doi:10.1213/ane.0000000000005017

Cited by 25 publications

(26 citation statements)

References 29 publications

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“…Butorphanol is known to act as a partial agonist of KOR in the G-protein activation signaling pathway (24). The results of western blot analysis revealed that LPS stimulation downregulated the expression levels of KOR in H9C2 cells, whereas the expression levels of KOR were upregulated following butorphanol treatment (Fig.…”

Section: Butorphanol Upregulates the Expression Of Kor In Lps-induced H9c2 Cellsmentioning

confidence: 90%

Butorphanol alleviates lipopolysaccharide‑induced inflammation and apoptosis of cardiomyocytes via activation of the κ‑opioid receptor

Tang

Luo

et al. 2021

Exp Ther Med

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Sepsis-induced myocardial dysfunction is a leading cause of the high mortality rates associated with sepsis. The aim of the present study was to investigate the effect of butorphanol on sepsis-induced cardiomyocyte dysfunction. Lipopolysaccharide (LPS) was used to induce H9C2 cardiomyocytes to establish an in vitro sepsis model. The effect of butorphanol on the viability of LPS-induced H9C2 cells was analyzed using a Cell Counting Kit-8 assay. The levels of tumor necrosis factor-α, interleukin (IL)-1β and IL-6 were detected using ELISA. Western blotting was used to analyze the expression levels of inflammation-and apoptosis-related proteins. Cell apoptosis was measured using a TUNEL assay. The expression levels of κ-opioid receptor (KOR) were analyzed using reverse transcription-quantitative PCR analysis and western blotting. Following LPS induction, the levels of inflammatory cytokines and proapoptotic proteins were found to be upregulated in H9C2 cells, while butorphanol treatment downregulated these levels. The expression levels of KOR were also upregulated following butorphanol treatment in LPS-induced H9C2 cells. Addition of the KOR inhibitor, nor-binaltorphimine, alleviated the inhibitory effects of butorphanol on inflammation and apoptosis in LPS-induced H9C2 cells. In conclusion, the findings of the present study provided evidence indicating that butorphanol may alleviate LPS-induced inflammation and apoptosis in cardiomyocytes by upregulating KOR expression, which may provide a novel insight into the potential therapeutic effects of butorphanol and its underlying mechanism of action.

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Section: Butorphanol Upregulates the Expression Of Kor In Lps-induced H9c2 Cellsmentioning

confidence: 90%

Butorphanol alleviates lipopolysaccharide‑induced inflammation and apoptosis of cardiomyocytes via activation of the κ‑opioid receptor

Tang

Luo

et al. 2021

Exp Ther Med

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“…Butorphanol is a partial μ-opioid receptor (MOR) agonist that also exhibits 20fold higher affinity for KOR. This synthetic opioid demonstrates higher potency and lower dependence when compared with morphine (54). Butorphanol is available as a narcotic analgesic in parenteral and transnasal formulations, although tolerability may be limited by central nervous effects including somnolence, nausea, and vomiting (55).…”

Section: κ-Opioid Agonistsmentioning

confidence: 99%

Receptor and Molecular Targets for the Development of Novel Opioid and Non-Opioid Analgesic Therapies

2021

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BACKGROUND: Although conventional pain relief therapeutics have centered around μ-opioid agonists, these drugs are limited by adverse side effects, including respiratory depression and addiction potential. The ongoing opioid epidemic has galvanized research into novel analgesic therapies with more favorable profiles. New pharmacologic agents have been developed to target neuronal pathways involved in pain sensation. Certain receptors have been recognized to mediate nociceptive transmission, central sensitization, and the development of chronic pain states. OBJECTIVES: We conducted a literature review to identify potential targets for novel analgesic therapies. STUDY DESIGN: This study is a narrative review of potential analgesic targets. We characterize their antinociceptive mechanisms of action and evaluate their therapeutic potential. METHODS: A systemized search of available literature on novel analgesics was performed. A search was performed through the PubMed database to identify articles with key words of “novel analgesics,” “novel non-opioid analgesics,” “novel pain targets,” and “non-opioid analgesics.” Potential drug classes were identified and researched through corresponding keywords, with an emphasis on publications from 2018 to 2020. Older articles were included if frequently referenced by current literature. RESULTS: Potential novel analgesic targets include Nav1.7, Nav1.8, CaV2.2, and transient receptor potential vanilloid-1 (TRPV1) cation channel receptors in the peripheral nervous system. Other approaches disrupt the synthesis of pronociceptive signaling molecules such as nitric oxide, prostaglandin E2, and interleukin-6 (IL-6). Within central pain pathways, modification of -opioid, -opioid, N-methyl-D-aspartate, and cannabinoid receptors have been investigated in chronic pain and hyperalgesia models. Recent advances in molecular technology have also presented opportunities to modify protein expression or the cellular genome altogether. LIMITATIONS: Several analgesic targets have only demonstrated efficacy in preclinical trials. There are limited data evaluating the long-term safety profiles of therapies further on in development. CONCLUSIONS: We provide an overview of potential analgesic therapies in various stages of development, which may become clinically relevant in the near future. Some drugs such as TRPV1 agonists, anti-IL-6, and anti-nerve growth factor antibodies have demonstrated analgesic effect in specific clinical pain states. KEY WORDS: Nav1.7, Cav2.2, TRPV1, mPGES-1, IL-6, FAAH, NGF, gene therapy

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“…Clinical drugs targeting KOR, such as oxycodone ( 178 ) and butorphanol ( 179 ), are KOR/MOR mixed agonists. Similar to morphine, oxycodone inhibits proliferation and migration of human lung adenocarcinoma cells and induces apoptosis ( 180 ).…”

Section: Effects Of Opioids On Tumorsmentioning

confidence: 99%

Opioids in cancer: The κ‑opioid receptor (Review)

et al. 2021

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The κ-opioid receptor (KOR) is one of the primary receptors of opioids and serves a vital role in the regulation of pain, anesthesia, addiction and other pathological and physiological processes. KOR is associated with several types of cancer and may influence cancer progression. It has been proposed that KOR may represent a new tumor molecular marker and provide a novel basis for molecular targeted therapies for cancer. However, the association between KOR and cancer remains to be explored comprehensively. The present review introduces KOR and its association with different types of cancer. Improved understanding of KOR may facilitate development of novel antitumor therapies. Contents1. Introduction 2. Discovery, structure and typing of KOR 3. Expression and physiological function of KOR 4. Expression, function and significance of KOR in various types of cancer 5. Potential roles of KOR in cancer 6. Effects of opioids on tumors 7. Conclusion and future prospects

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Molecular Interaction Between Butorphanol and κ-Opioid Receptor

Cited by 25 publications

References 29 publications

Butorphanol alleviates lipopolysaccharide‑induced inflammation and apoptosis of cardiomyocytes via activation of the κ‑opioid receptor

Butorphanol alleviates lipopolysaccharide‑induced inflammation and apoptosis of cardiomyocytes via activation of the κ‑opioid receptor

Receptor and Molecular Targets for the Development of Novel Opioid and Non-Opioid Analgesic Therapies

Opioids in cancer: The κ‑opioid receptor (Review)

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