Inhibitive effect of loureirin B plus capsaicin on tetrodotoxin-resistant sodium channel

OBJECTIVE: To investigate whether the effect of loureirin B plus capsaicin on tetrodotoxin-resistant（TTX-R） sodium channel.METHODS: By using whole-cell patch-clamp recordings, in acutely isolated dorsal root ganglion（DRG） neurons, the combined effects of loureirin B and capsaicin on TTX-R sodium channel were observed. Based on the data, the interaction between loureirin B and capsaicin in their modulation on TTX-R sodium channel was assessed.RESULTS: Loureirin B could not induce transient inward TRPV1 current. Capsazepine, a transient receptor potential vanilloid l（TRPV1） antagonist, could not attenuate the block of 0.64 mmol/L loureirin B on TTX-R sodium channel. There was no significant difference（P > 0.05） between IC;of loureirin B（0.37 mmol/L） on TTX-R sodium channel in capsaicin-sensitive DRG neurons and that（0.38 mmol/L）in capsaicin-insensitive DRG neurons. However,there was a significant difference（P < 0.05） between the IC;of capsaicin（0.28 μmol/L） on TTX-R sodium channel in capsaicin-sensitive DRG neurons and that（52.24 μmol/L） in capsaicin-insensitive DRG neurons. Four combinations composed of various concentrations of loureirin B and capsaicin could all inhibit TTX-R sodium currents but have different interactions between loureirin B and capsaicin.CONCLUSION: Loureirin B plus capsaicin could produce double blockage on TRPV1 and modulation on TTX-R sodium channel. The action of loureirin B onTTX-R sodium channel was independent ofTRPV1 but similar with that of capsaicin on TTX-R sodium channel in capsaicin-insensitive DRG neurons.