Session
Speaker
Loureirin B: A novel chemical component which can modulate
voltage-gated sodium currents through TRPV1 receptor
M. Zhinan China
Dragon's Blood is one of the renowned traditional medicines with analgesic
activity. Loureirin B is a flavonoid component extracted from dragon's
blood and is used as the marker substance for its quality control.
To explore the analgetic mechanism of dragon's blood, the effects
of loureirin B on the tetrodotoxin-sensitive and tetrodotoxin-resistant
voltage-gated sodium currents in dorsal root ganglion neurons were
observed by using patch clamp technique. Results showed that loureirin
B could modulate the above two types of the voltage-gated sodium currents
in dorsal root ganglion neurons. It can be inferred that loureirin
B could directly interfere with the transmission of nociceptive information
in primary sensory neurons by modulating sodium channels. This viewpoint
has been verified by the in vivo experimental results. Loureirin B
could inhibit the discharge activities of wide dynamic range (WDR)
neurons in spinal dorsal horn (SDH) of intact male Wistar rats evoked
by electric stimulation at sciatic nerve. But the mechanism of the
modulation of loureirin B on the voltage-gated sodium currents is
still unclear. However, it is remarkable that the chemical structures
of capsaicin and loureirin B are similar. It has been proved by experiments
that capsaicin could inhibit the action potentials and voltage-gated
sodium channels in capsaicin-sensitive trigeminal ganglion neurons.
Moreover, the selective effect of capsaicin on voltage-gated sodium
channels was reversed in transient receptor potential vanilloid subtype
1 (TRPV1) -/- mice, which suggested that this effect was dependent
on TRPV1 receptor. TRPV1 is known as capsaicin receptor and activated
by capsaicin. From the above, it can be seen that there are some similarities
between the mechanism of capsaicin modulating sodium channels and
that of loureirin B. To verify our conjecture, the effect of loureirin
B on TRPV1 receptor and the modulation of the combination of loureirin
B and capsaicin on the sodium channels in acutely isolated rat DR
G neurons were observed by using patch clamp technique. Results showed
that loureirin B could inhibit both the capsaicin-activated currents
and the capsaicin-evoked depolarization in DRG neurons, which indicated
that loureirin B could modulate TRPV1 receptor. Although the combination
of loureirin B and capsaicin could inhibit the voltage-gated sodium
currents in DRG neurons, the inhibition degree of the combination
was lower than that of each component. If there is only additive interaction
between the two components, the more inhibition degree on the voltage-gated
sodium currents should be induced by the combination of capsaicin
and loureirin B than each component used alone. It suggested that
the effect of loureirin B on the voltage-gated sodium currents in
DRG neurons was antagonized by capsaicin. The inhibition mechanism
of loureirin B on the voltage-gated sodium currents should be consistent
with that of capsaicin. Since loureirin B and capsaicin could competitive
binding to the TRPV1 receptor, the inhibition degree of loureirin
B on the voltage-gated sodium currents was weakened by capsaicin.
Besides of capsaicin, loureirin B perhaps should become a novel chemical
component which can modulate voltage-gated sodium currents through
TRPV1 receptor.
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