Capsaicin-stimulated release of substance P from cultured dorsal root ganglion neurons: Involvement of two distinct mechanisms

Capsaicin, the pungent component of "hot" chilli peppers, selectively activ ates a distinct population of primary sensory neurons responsive to noxious stimuli. Many of these fibres express neuropeptides including the tachykin in, substance P. Using cultured dorsal root ganglion neurons, we found that capsaicin (10 mu M) stimulated a 2-fold increase in release of substance P in the absence of extracellular Ca2+. Elevated potassium (75 mM) was unabl e to induce release under these conditions. The introduction of Ca2+ enhanc ed capsaicin-induced release and brought about a robust response to potassi um. Preincubation of cells with botulinum neurotoxin A (100 nM) completely blocked potassium-induced release but the capsaicin response, in the absenc e of Ca2+, was unaffected. However, toxin treatment dramatically reduced ca psaicin-stimulated release in the presence of Ca2+. It is concluded that ca psaicin induces release of substance P from dorsal root ganglion neurons vi a two mechanisms, one requiring extracellular Ca2+ and the intact synaptoso mal-associated protein 25 kDa (SNAP-25), and the other independent of extra cellular Ca2+ and not involving SNAP-25. BIOCHEM PHARMACOL 59;11:1403-1406, 2000. (C) 2000 Elsevier Science Inc.