Parecoxib, a selective blocker of cyclooxygenase-2, directly inhibits neuronal delayed-rectifier K+ current, M-type K+ current and Na+ current

Yuan Yuarn Liu, Hung-Tsung Hsiao, Jeffrey Chi Fei Wang, Yen-Chin Liu, Sheng-Nan Wu

研究成果: Article

4 引文 (Scopus)

摘要

Parecoxib, a prodrug of valdecoxib, is a selective inhibitor of cyclooxygenase-2 and widely used for traumatic and postoperative patients to avoid opioid-induced side effects. It is a potent analgesic and has a role in multimodal analgesic and enhanced recovery after surgery. Whether parecoxib exerts any actions on these types of ionic currents remains unclear. In this study, we investigated whether it exerts any effects on ion currents in differentiated NG108-15 neuronal cells. Cell exposure to parecoxib (1–30 μM) caused a reversible reduction in the amplitude of IK(DR) with an IC50 value of 9.7 μM. The time course for the IK(DR) inactivation in response to a long-lasting pulse was changed to the biexponential process during cell exposure to 3 μM parecoxib. Other agents known to inhibit the cyclooxygenase activity have minimal effects on IK(DR). Parecoxib enhanced the degree of excessive accumulative inhibition of IK(DR) inactivation evoked by a train of brief repetitive stimuli. This compound suppressed the amplitude of M-type K+ current. It depressed the peak amplitude of voltage-gated Na+ current with no change in the current-voltage relationship of this current. However, it did not have any effect on hyperpolarization-activated cation current. No change in the expression level of KV3.1 mRNA was detected in the presence of parecoxib. The effects of parecoxib on ion currents are direct and unrelated to its inhibition of the enzymatic activity of cyclooxygenase-2. The inhibition of these ion channels by parecoxib may partly contribute to the underlying mechanisms by which it affects neuronal function in vivo.

原文English
頁(從 - 到)95-101
頁數7
期刊European Journal of Pharmacology
844
DOIs
出版狀態Published - 2019 二月 5

指紋

Cyclooxygenase 2
Analgesics
Ions
parecoxib
Cyclooxygenase 2 Inhibitors
Prodrugs
Prostaglandin-Endoperoxide Synthases
Ion Channels
Opioid Analgesics
Inhibitory Concentration 50
Cations
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Pharmacology

引用此文

@article{384c0d3cce2c43c3bd952ddeb51c3d19,
title = "Parecoxib, a selective blocker of cyclooxygenase-2, directly inhibits neuronal delayed-rectifier K+ current, M-type K+ current and Na+ current",
abstract = "Parecoxib, a prodrug of valdecoxib, is a selective inhibitor of cyclooxygenase-2 and widely used for traumatic and postoperative patients to avoid opioid-induced side effects. It is a potent analgesic and has a role in multimodal analgesic and enhanced recovery after surgery. Whether parecoxib exerts any actions on these types of ionic currents remains unclear. In this study, we investigated whether it exerts any effects on ion currents in differentiated NG108-15 neuronal cells. Cell exposure to parecoxib (1–30 μM) caused a reversible reduction in the amplitude of IK(DR) with an IC50 value of 9.7 μM. The time course for the IK(DR) inactivation in response to a long-lasting pulse was changed to the biexponential process during cell exposure to 3 μM parecoxib. Other agents known to inhibit the cyclooxygenase activity have minimal effects on IK(DR). Parecoxib enhanced the degree of excessive accumulative inhibition of IK(DR) inactivation evoked by a train of brief repetitive stimuli. This compound suppressed the amplitude of M-type K+ current. It depressed the peak amplitude of voltage-gated Na+ current with no change in the current-voltage relationship of this current. However, it did not have any effect on hyperpolarization-activated cation current. No change in the expression level of KV3.1 mRNA was detected in the presence of parecoxib. The effects of parecoxib on ion currents are direct and unrelated to its inhibition of the enzymatic activity of cyclooxygenase-2. The inhibition of these ion channels by parecoxib may partly contribute to the underlying mechanisms by which it affects neuronal function in vivo.",
author = "Liu, {Yuan Yuarn} and Hung-Tsung Hsiao and Wang, {Jeffrey Chi Fei} and Yen-Chin Liu and Sheng-Nan Wu",
year = "2019",
month = "2",
day = "5",
doi = "10.1016/j.ejphar.2018.12.005",
language = "English",
volume = "844",
pages = "95--101",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",

}

TY - JOUR

T1 - Parecoxib, a selective blocker of cyclooxygenase-2, directly inhibits neuronal delayed-rectifier K+ current, M-type K+ current and Na+ current

AU - Liu, Yuan Yuarn

AU - Hsiao, Hung-Tsung

AU - Wang, Jeffrey Chi Fei

AU - Liu, Yen-Chin

AU - Wu, Sheng-Nan

PY - 2019/2/5

Y1 - 2019/2/5

N2 - Parecoxib, a prodrug of valdecoxib, is a selective inhibitor of cyclooxygenase-2 and widely used for traumatic and postoperative patients to avoid opioid-induced side effects. It is a potent analgesic and has a role in multimodal analgesic and enhanced recovery after surgery. Whether parecoxib exerts any actions on these types of ionic currents remains unclear. In this study, we investigated whether it exerts any effects on ion currents in differentiated NG108-15 neuronal cells. Cell exposure to parecoxib (1–30 μM) caused a reversible reduction in the amplitude of IK(DR) with an IC50 value of 9.7 μM. The time course for the IK(DR) inactivation in response to a long-lasting pulse was changed to the biexponential process during cell exposure to 3 μM parecoxib. Other agents known to inhibit the cyclooxygenase activity have minimal effects on IK(DR). Parecoxib enhanced the degree of excessive accumulative inhibition of IK(DR) inactivation evoked by a train of brief repetitive stimuli. This compound suppressed the amplitude of M-type K+ current. It depressed the peak amplitude of voltage-gated Na+ current with no change in the current-voltage relationship of this current. However, it did not have any effect on hyperpolarization-activated cation current. No change in the expression level of KV3.1 mRNA was detected in the presence of parecoxib. The effects of parecoxib on ion currents are direct and unrelated to its inhibition of the enzymatic activity of cyclooxygenase-2. The inhibition of these ion channels by parecoxib may partly contribute to the underlying mechanisms by which it affects neuronal function in vivo.

AB - Parecoxib, a prodrug of valdecoxib, is a selective inhibitor of cyclooxygenase-2 and widely used for traumatic and postoperative patients to avoid opioid-induced side effects. It is a potent analgesic and has a role in multimodal analgesic and enhanced recovery after surgery. Whether parecoxib exerts any actions on these types of ionic currents remains unclear. In this study, we investigated whether it exerts any effects on ion currents in differentiated NG108-15 neuronal cells. Cell exposure to parecoxib (1–30 μM) caused a reversible reduction in the amplitude of IK(DR) with an IC50 value of 9.7 μM. The time course for the IK(DR) inactivation in response to a long-lasting pulse was changed to the biexponential process during cell exposure to 3 μM parecoxib. Other agents known to inhibit the cyclooxygenase activity have minimal effects on IK(DR). Parecoxib enhanced the degree of excessive accumulative inhibition of IK(DR) inactivation evoked by a train of brief repetitive stimuli. This compound suppressed the amplitude of M-type K+ current. It depressed the peak amplitude of voltage-gated Na+ current with no change in the current-voltage relationship of this current. However, it did not have any effect on hyperpolarization-activated cation current. No change in the expression level of KV3.1 mRNA was detected in the presence of parecoxib. The effects of parecoxib on ion currents are direct and unrelated to its inhibition of the enzymatic activity of cyclooxygenase-2. The inhibition of these ion channels by parecoxib may partly contribute to the underlying mechanisms by which it affects neuronal function in vivo.

UR - http://www.scopus.com/inward/record.url?scp=85058154105&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058154105&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2018.12.005

DO - 10.1016/j.ejphar.2018.12.005

M3 - Article

C2 - 30529469

AN - SCOPUS:85058154105

VL - 844

SP - 95

EP - 101

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

ER -