Capsaicin-induced depolarisation of mitochondria in dorsal root ganglion neurons is enhanced by vanilloid receptors

Capsaicin, a pungent ingredient of hot chilli peppers, triggered Ca2+ influ x in dorsal root ganglion (DRG) neurons, which express specific vanilloid r eceptors of type 1, with ED50 < 100 nM. An increase in capsaicin concentrat ion to 10 <mu>M inhibited Ca2+ clearance from the cytosol, but did not affe ct the amplitude of intracellular Ca2+ elevation. In DRG neurons, 10 muM ca psaicin also produced a significant drop in mitochondrial membrane potentia l (Delta psi), as measured with the mitochondria-specific potentiometric fl uorescent dye JC-1. Similar loss of mitochondrial potential upon applicatio n of capsaicin was observed in non-neuronal primary (human lymphocytes) and transformed (human myeloid leukaemia cell line, HL-60) cells. The EC50 val ues for capsaicin-induced mitochondrial depolarisation were 6.9 muM (DRG ne urons), 200 muM (human lymphocytes) and 150 muM (HL-60 cells). Removal of e xtracellular Ca2+ or an application of the antioxidant trolox attenuated ca psaicin-induced dissipation of Delta psi in DRG neurons, but not in human l ymphocytes and HL-60 cells. Rotenone, an inhibitor of complex I of the mito chondrial respiratory chain, and oligomycin, an inhibitor of F0F1-ATPase, s ignificantly enhanced the mitochondrial depolarisation produced by capsaici n in DRG neurons. In human lymphocytes and HL-60 cells, only oligomycin pot entiated the effect of capsaicin. From our results, we suggest that, in DRG neurons and non-neuronal cells, c apsaicin dissipates Delta psi, possibly due to a direct inhibition or compl ex I of the mitochondrial respiratory chain. The presence of vanilloid rece ptor-1 in DRG neurons makes their mitochondria 20-30-fold more sensitive to the depolarising effect of capsaicin compared with non-neuronal cells lack ing vanilloid receptor-1. The higher sensitivity of DRG neurons to capsaici n may underlie a selective neurotoxicity of capsaicin towards sensory neuro ns. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.