Characterization of functional vanilloid receptors expressed by mast cells

Capsaicin and its ultrapotent analog resiniferatoxin (RTX) act through specific vanilloid receptors on sensory neurons. The C-type receptor is coupled to ⁴⁵Ca uptake, whereas the R-type is detectable by [³H]RTX binding. We describe here specific vanilloid responses in murine mast cells (MCs). In the MC lines and in bone marrow-derived mast cells, capsaicin and RTX induced ⁴⁵Ca uptake similarly to that observed for cultured rat dorsal root ganglion neurons (DRGs). This response was antagonized by the antagonists capsazepine and ruthenium red. As in DRGs, pretreatment of MCs with capsaicin or RTX induced desensitization to subsequent stimulation of ⁴⁵Ca uptake. The potency for desensitization by RTX in the MCs corresponded to that for ⁴⁵Ca uptake, whereas in DRGs it occurred at significantly lower concentrations corresponding to that for the high-affinity [³H]RTX binding site. Consistent with this difference, in MCs we were unable to detect [³H]RTX binding. Vanilloids were noncytotoxic to the MCs, in contrast to the DRGs. Although vanilloids did not cause degranulation in MCs, in the P815 clone capsaicin evoked selective interleukin-4 release. We conclude that certain MCs possess vanilloid receptors, but only the C-type that functions as a channel. Our finding that MCs can respond directly to capsaicin necessitates a reevaluation of the in vivo pathway of inflammation in response to vanilloids.