Modulation on tetrodotoxin‐resistant sodium current of loureirin B in rat dorsal root ganglion neurons via cyclic AMP–dependent protein kinase A

To search the modulation mechanism of loureirin B, a flavonoid is extracted from Dracaena cochinchinensis, on tetrodotoxin‐resistant (TTX‐R) sodium channel in dorsal root ganglion (DRG) neurons of rats. Experiments were carried out based on patch‐clamp technique and molecular biological methods. We observed the time‐dependent inhibition of loureirin B on TTX‐R sodium currents in DRG neurons and found that neither occupancy theory nor rate theory could well explain the time‐dependent inhibitory effect of loureirin B on TTX‐R sodium currents. It suggested that a second messenger‐mediated signaling pathway may be involved in the modulation mechanism. So the cyclin AMP (cAMP) level of the DRG neurons before and after incubation with loureirin B was tested by ELISA Kit. Results showed that loureirin B could increase the cAMP level and the increased cAMP was caused by the enhancement of adenylate cyclase (AC) induced by loureirin B. Immunolabelling experiments further confirmed that loureirin B can promote the production of PKA in DRG neurons. In the presence of the PKA inhibitor H‐89, the inhibitory effect of loureirin B on TTX‐R sodium currents was reversed. Forskolin, a tool in biochemistry to raise the levels of cAMP, also could reduce TTX‐R sodium currents similar to that of loureirin B. These studies demonstrated that loureirin B can modulate the TTX‐R sodium channel in DRG neurons via an AC/cAMP/PKA pathway involving the activation of AC and PKA, which also can be used to explain the other pharmacological effects of loureirin B. Loureirin B can modulate the tetrodotoxin‐resistant (TTX‐R) sodium channel in DRG neurons via an AC/cAMP/PKA pathway involving the activation of AC and PKA, which also can be used to explain the other pharmacological effects of loureirin B.