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• W2146280108 abstract "Background and Purpose The P 2 X 7 receptor is an ATP ‐gated ion channel predominantly expressed in immune cells and plays a key role in inflammatory processes. Ginseng is a well‐known C hinese herb with both pro‐ and anti‐inflammatory properties and many of its actions have been ascribed to constituent ginsenosides. We screened a number of ginsenoside compounds for pharmacological activity at P 2 X 7 receptors, that might contribute to the reported immunomodulatory actions of ginseng. Experimental Approach We used several assays to measure responses of P 2 X 7 receptors, ATP ‐mediated dye uptake, intracellular calcium measurement and whole‐cell patch‐clamp recordings. HEK ‐293 cells stably expressing human P 2 X 7 receptors were used in addition to mouse macrophages endogenously expressing P 2 X 7 receptors. Key Results Four ginsenosides of the protopanaxdiol series, R b1, R h2, Rd and the metabolite compound K ( CK ) potentiated the dye uptake responses of P 2 X 7 receptors, whereas other ginsenosides tested were ineffective (1–10 μM). The potentiation was rapid in onset, required a threshold concentration of ATP (>50 μM) and had an EC 50 of 1.08 μM. CK markedly enhanced ATP ‐activated P 2 X 7 currents, probably via an extracellular site of action. One of the consequences of this potentiation effect is a sustained rise in intracellular Ca 2+ that could account for the decrease in cell viability in mouse macrophages after a combination of 500 μM ATP and 10 μM CK that are non‐toxic when applied alone. Conclusions and Implications This study identifies selected ginsenosides as novel potent allosteric modulators of P 2 X 7 channels that may account for some of the reported immune modulatory actions of protopanaxdiol ginsenosides in vivo ." @default.
• W2146280108 created "2016-06-24" @default.
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• W2146280108 date "2015-04-24" @default.
• W2146280108 modified "2023-10-17" @default.
• W2146280108 title "Selected ginsenosides of the protopanaxdiol series are novel positive allosteric modulators of P2X7 receptors" @default.
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• W2146280108 doi "https://doi.org/10.1111/bph.13123" @default.
• W2146280108 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4500369" @default.
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