ACTIVATION OF PROTEIN-KINASE-C BY THE CAPSAICIN ANALOG RESINIFERATOXIN IN SENSORY NEURONS

Resiniferatoxin and capsaicin are sensory neurone-specific excitotoxin s that operate a common cation channel in nociceptors. Resiniferatoxin is structurally similar to capsaicin and to phorbol esters. Specific [H-3]-resiniferatoxin binding, which was detected in the membrane (K-D value 1.8 +/- 0.2 nM) but not cytosolic fraction of rat dorsal root g anglia, could not be displaced by phorbol 12,13-dibutyrate. Conversely , resiniferatoxin did not displace [H-3]phorbol 12,13-dibutyrate bindi ng in either the cytosolic or membrane fraction. Resiniferatoxin and c apsaicin both caused translocation of protein kinase C in dorsal root ganglion neurones (EC(50) value 18 +/- 3 nM). This translocation was g reatly reduced but not abolished, in the absence of external Ca2+, sug gesting that it was secondary to Ca2+ entry. Resiniferatoxin also caus ed direct activation of a Ca2+- and lipid-dependent kinase (or kinases ) in the cytosolic fraction of dorsal root ganglia, at concentrations (100 nM to 10 mu M) higher than required for displacement of [H-3]resi niferatoxin binding or translocation of protein kinase C. Capsaicin (u p to 10 mu M) was unable to mimic this effect. These data imply that a lthough resiniferatoxin-induced translocation of protein kinase C in d orsal root ganglion neurones was mainly indirect, it also caused direc t activation of a protein kinase C-like kinase in these cells.