Endothelin Receptor-mediated Responses in Trigeminal Ganglion Neurons

Abstract

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_A and ET_B and endothelin-induced responses in rat TRG neurons. Double-immunofluorescence studies demonstrated that ET_A and ET_B were expressed in TRG neurons and that 26% of ET_A- or ET_B-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_A antagonist BQ-123, but not by the ET_B antagonist BQ-788. Ca²⁺-imaging showed that endothelin-1 increased the intracellular Ca²⁺ concentration in more than 20% of the dissociated neurons. Importantly, unlike the effect of endothelin-1 on capsaicin-induced current, the Ca²⁺ response was largely suppressed by BQ-788 but not by BQ-123. These results suggest that ET_A-mediated TRPV1 hyperactivation via PKC activation and ET_B-mediated Ca²⁺ mobilization occurs in different subsets of TRG neurons. These endothelin-induced responses may contribute to the induction of orofacial pain. The ET_B-mediated function in TRG neurons is a special feature in the trigeminal system because of no ET_B expression in dorsal root ganglion neurons.