Recent evidence implicates
endothelin in nociception, but it is unclear how
endothelin activates trigeminal ganglion (TRG) neurons. In the present study, we investigated the expression of the
endothelin receptors ETA and ETB and
endothelin-induced responses in rat TRG neurons. Double-immunofluorescence studies demonstrated that ETA and ETB were expressed in TRG neurons and that 26% of ETA- or ETB-expressing neurons expressed both receptors. During whole-cell patch-clamp recording,
endothelin-1 enhanced an induced current in response to
capsaicin, a TRPV1 agonist, in approximately 20% of dissociated neurons. The enhancement was blocked by the PKC inhibitor
chelerythrine and by the ETA antagonist
BQ-123, but not by the ETB antagonist
BQ-788. Ca(2+)-imaging showed that
endothelin-1 increased the intracellular Ca(2+) concentration in more than 20% of the dissociated neurons. Importantly, unlike the effect of
endothelin-1 on
capsaicin-induced current, the Ca(2+) response was largely suppressed by
BQ-788 but not by
BQ-123. These results suggest that ETA-mediated TRPV1 hyperactivation via PKC activation and ETB-mediated Ca(2+) mobilization occurs in different subsets of TRG neurons. These
endothelin-induced responses may contribute to the induction of
orofacial pain. The ETB-mediated function in TRG neurons is a special feature in the trigeminal system because of no ETB expression in dorsal root ganglion neurons.