Pseudoginsenoside-F11 attenuates morphine-induced signalling in Chinese hamster ovary-mu cells.
Pseudoginsenoside-F11 (PF11), an ocotillol type saponin isolated from Panax quinquefolium L., has been shown to antagonize the behavioral actions of morphine. Biochemical experiments revealed that PF11 could inhibit diprenorphine (DIP) binding with an IC50 of approximately 6.1 microM and reduced the binding potency of morphine in Chinese hamster ovary (CHO)-mu cells. Furthermore, PF11 significantly attenuated morphine-stimulated [35S]GTPgammaS binding in a dose dependent manner, and strongly decreased the efficacy of morphine to inhibit intracellular cAMP production. In addition, PF11 pretreatment could also significantly inhibit naloxone induced cAMP overshoot in the morphine-pretreated cells. However, PF11 per se had no effect on either [35S]GTPgammaS binding or intracellular cAMP accumulation. These data suggested that PF11 antagonized the morphine stimulated opioid receptor signalling directly at the cellular level.
Li
Z
Z
Department of Pharmacology, Shenyang Pharmaceutical University, PR China.
Xu
N J
NJ
Wu
C F
CF
Xiong
Y
Y
Fan
H P
HP
Zhang
W B
WB
Sun
Y
Y
Pei
G
G
D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D016466:CHO Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D000242:Cyclic AMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D036145:Ginsenosides; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000493:pharmacokinetics; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics; D009021:Morphine Dependence / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013462:Sulfur Radioisotopes / Q000493:pharmacokinetics
D000701:Analgesics, Opioid; D036145:Ginsenosides; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D012503:Saponins; D013462:Sulfur Radioisotopes; C413985:pseudoginsenoside F11; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D009020:Morphine; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases