Activation of opioid mu-receptor by sinomenine in cell and mice.
Sinomenine, one of the alkaloids extracted from roots or stems of Sinomenium acutum, is documented to show antinociceptive action but the action mechanism is still unclear. The present study was aimed to investigate the effect of sinomenine on opioid mu-receptor (OMR). In Chinese Hamster Ovary (CHO) cell transfected with OMR, the binding of [(3)H]naloxone was displaced by sinomenine in a concentration-dependent manner. This compound also raised the phosphorylation of OMR in these cells. In a tail-flick test, sinomenine produced dose-dependent antinociception in mice, which was dose-dependently inhibited by pretreatment of naloxonazine, a selective OMR antagonist. Long-term pretreatment with sinomenine may delay the analgesic tolerance of morphine. The obtained results suggest that sinomenine has an ability to activate OMR, implicating the potential of sinomenine to be applied in clinic.
Wang
Mao Hsien
MH
Department of Anesthesiology, En-Chu-Kon Hospital, Sanxia Town, Taipei County, Taiwan.
Chang
Cheng-Kuei
CK
Cheng
Jun-Hwa
JH
Wu
Hung-Tsung
HT
Li
Ying-Xiao
YX
Cheng
Juei-Tang
JT
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009019:Morphinans / Q000737:chemistry / Q000494:pharmacology*; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D000701:Analgesics, Opioid; D009019:Morphinans; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009270:Naloxone; C009271:sinomenine; D009020:Morphine