TY - JOUR
T1 - μ-Opioid receptor-independent fashion of the suppression of sodium currents by μ-opioid analgesics in thalamic neurons
AU - Hashimoto, Keisuke
AU - Amano, Taku
AU - Kasakura, Akiko
AU - Uhl, George R.
AU - Sora, Ichiro
AU - Sakai, Norio
AU - Kuzumaki, Naoko
AU - Suzuki, Tsutomu
AU - Narita, Minoru
PY - 2009/3/27
Y1 - 2009/3/27
N2 - Most reports in the literature have shown that the effects of opioid analgesics are primarily mediated by μ-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 μ-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.
AB - Most reports in the literature have shown that the effects of opioid analgesics are primarily mediated by μ-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 μ-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.
KW - Fentanyl
KW - Lidocaine
KW - Morphine
KW - Oxycodone
KW - Voltage-gated sodium channels
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U2 - 10.1016/j.neulet.2009.01.066
DO - 10.1016/j.neulet.2009.01.066
M3 - Article
C2 - 19429017
AN - SCOPUS:60949090927
VL - 453
SP - 62
EP - 67
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 1
ER -