K252A MODULATES THE EXPRESSION OF NERVE GROWTH FACTOR-DEPENDENT CAPSAICIN SENSITIVITY AND SUBSTANCE-P LEVELS IN CULTURED ADULT-RAT DORSAL-ROOT GANGLION NEURONS

K252a, an inhibitor of trk phosphorylation and nerve growth factor sig nal transduction in PC12 cells, blocked nerve growth factor-induced re sponses in cultured adult rat dorsal root ganglion sensory neurones. T he nerve growth factor-dependent appearance of capsaicin sensitivity a nd accumulation of the neuropeptide substance P were inhibited when do rsal root ganglion neurones were grown in the presence of low concentr ations (100 nM) of K252a. At higher concentrations (3 mu M), however, K252a stimulated the development of capsaicin sensitivity and the accu mulation of substance P even in the absence of nerve growth factor. By using a wide dose range, therefore, we showed that K252a could either inhibit or mimic nerve growth factor's actions on sensory neurones. T hese results may explain the apparent paradox in the literature that s ome groups show a blocking effect of K252a on nerve growth factor-depe ndent survival of dorsal root ganglion sensory neurones, whereas other s report that K252a can substitute for nerve growth factor or other tr ophic factors and promote neuronal survival.