SPECIFIC VANILLOID RESPONSES IN C6 RAT GLIOMA-CELLS

Capsaicin and its ultrapotent analog resiniferatoxin (RTX) act through specific vanilloid receptors on sensory neurons. Here, we describe sp ecific vanilloid responses in rat C6 glioma cells. Capsaicin and RTX s timulated Ca-45 uptake in a similar fashion to that found for cultured rat dorsal root ganglion neurons (DRGs); this response was antagonize d by the antagonists capsazepine and ruthenium red. As in DRGs, pretre atment of C6 cells with capsaicin or RTX produced desensitization to s ubsequent stimulation of Ca-45 uptake. The potency for desensitization by RTX in the C6 cells corresponded to that for Ca-45 uptake, whereas in DRGs it occurred at significantly lower concentrations correspondi ng to that for the high affinity [H-3]RTX binding site. Consistent wit h this difference, in C6 cells we were unable to detect [H-3]RTX bindi ng. These characteristics suggest the presence of C-type but not R-typ e vanilloid receptors on C6 cells. After 2 day treatment, capsaicin bu t not RTX inhibited the proliferation and altered the differentiation of the cells and produced apoptosis. In the long term experiments, cap sazepine, instead of antagonizing the effect of capsaicin, acted as an agonist. Moreover, capsazepine displayed these effects with higher po tency than that of capsaicin. The different potencies and structure ac tivity relations suggest a distinct mechanism for these long-term vani lloid effects. Our finding that C6 cells can respond directly to capsa icin necessitates a reevaluation of the in vivo pathway of response to vanilloids, and highlights the importance of the neuron-glial network . (C) 1998 Elsevier Science B.V.