Pseudoginsenoside-F₁₁ attenuates morphine-induced signalling in Chinese hamster ovary-μ 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 ∼6.1 μM and reduced the binding potency of morphine in Chinese hamster ovary (CHO)-μ cells. Furthermore, PF₁₁ significantly attenuated morphine-stimulated [³⁵S]GTPγS 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]GTPγS binding or intracellular cAMP accumulation. These data suggested that PF₁₁ antagonized the morphine stimulated opioid receptor signalling directly at the cellular level.