Capsaicin-induced death of cultured neurons of the rat hippocampus

We studied the effects of an agonist of vanilloid receptors (VRs), capsaicin, and of an antagonist of VRs of type 1, capsazepin, on cultured neurons of the rat hippocampus. In cultures incubated for 1 day in a medium containing 10 µM capsaicin, the numbers of cytologically normal cells and those with manifestations of necrosis and apoptosis were, on average, 46.4 ± 3.3, 30.7 ± 2.4, and 22.9 ± 5.4%. The latter two values were more than three times greater than the respective indices under control conditions ( P < 0.05). Coincubation of the cells with 10 µM capsaicin and 25 µM capsazepin decreased the normalized number of apoptotic units by about one-third, while the number of cells with necrotic changes showed nearly no changes. Using confocal microscopy and staining the cells with a fluorescent dye, JC-1, we found that incubation with capsaicin resulted in a dramatic drop in the mitochondrial potential in the great majority of cultured cells, while capsazepin somewhat smoothed this effect. Thus, our data show that the cytotoxic effect of capsaicin is related to changes in the mitochondrial potential and is at least partially mediated by activation of type-1 VRs.