μ-Opioid receptor-independent fashion of the suppression of sodium currents by μ-opioid analgesics in thalamic neurons

NEUROSCIENCE LETTERS

卷:453

Article

Hashimoto, Keisuke¹  Amano, Taku^1,2  Kasakura, Akiko¹  Uhl, George R.³  Sora, Ichiro⁴  Sakai, Norio²  Kuzumaki, Naoko¹  Suzuki, Tsutomu¹  Narita, Minoru¹ 

[1] Hoshi Univ, Dept Toxicol, Sch Pharm & Pharmaceut Sci, Shinagawa Ku, Tokyo 1428501, Japan

[2] Hiroshima Univ, Dept Mol & Pharmacol Neurosci, Div Integrated Med Sci, Grad Sch Biomed Sci,Minami Ku, Hiroshima 7348551, Japan

[3] NIDA, Intramural Res Program, Baltimore, MD 21224 USA

[4] Tohoku Univ, Grad Sch Med, Dept Biol Psychiat, Sendai, Miyagi 9808574, Japan

关键词: Morphine;    Fentanyl;    Oxycodone;    Lidocaine;    Voltage-gated sodium channels;   

DOI  :  10.1016/j.neulet.2009.01.066

来源: Elsevier

【 摘 要 】

Most reports in the literature have shown that the effects of opioid analgesics are primarily mediated by mu-opioid receptor (MOR), whereas other potential targets of opioid analgesics have not been thoroughly characterized. In this study, we found that extracellular application of morphine, fentanyl or oxycodone,which are all considered to be MOR agonists, at relatively high concentrations, but not endogenous mu-opioid peptides, produced a concentration-dependent suppression of sodium currents in cultured thalamic neurons. These effects of opioids were not affected by either a MOR antagonist naloxone or a deletion of MOR gene. Among these opioids, fentanyl strongly suppressed sodium currents to the same degree as lidocaine, and both morphine and oxycodone slightly but significantly reduced sodium currents when they were present extracellularly. In contrast, the intracellular application of morphine, but not oxycodone, fentanyl or lidocaine, reduced sodium currents. These results suggest that morphine, fentanyl and oxycodone each produce the MOR-independent suppression of sodium currents by distinct mechanisms in thalamic neurons. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

Free