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_(50) 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_(50) 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.