Beschreibung:
<jats:p> 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 ET<jats:sub>A</jats:sub> and ET<jats:sub>B</jats:sub> and endothelin-induced responses in rat TRG neurons. Double-immunofluorescence studies demonstrated that ET<jats:sub>A</jats:sub> and ET<jats:sub>B</jats:sub> were expressed in TRG neurons and that 26% of ET<jats:sub>A</jats:sub>- or ET<jats:sub>B</jats:sub>-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 ET<jats:sub>A</jats:sub> antagonist BQ-123, but not by the ET<jats:sub>B</jats:sub> antagonist BQ-788. Ca<jats:sup>2+</jats:sup>-imaging showed that endothelin-1 increased the intracellular Ca<jats:sup>2+</jats:sup> concentration in more than 20% of the dissociated neurons. Importantly, unlike the effect of endothelin-1 on capsaicin-induced current, the Ca<jats:sup>2+</jats:sup> response was largely suppressed by BQ-788 but not by BQ-123. These results suggest that ET<jats:sub>A</jats:sub>-mediated TRPV1 hyperactivation via PKC activation and ET<jats:sub>B</jats:sub>-mediated Ca<jats:sup>2+</jats:sup> mobilization occurs in different subsets of TRG neurons. These endothelin-induced responses may contribute to the induction of orofacial pain. The ET<jats:sub>B</jats:sub>-mediated function in TRG neurons is a special feature in the trigeminal system because of no ET<jats:sub>B</jats:sub> expression in dorsal root ganglion neurons. </jats:p>