A new teleocidin analog from Streptomyces sp. MM216-87F4 induces substance P release from rat dorsal root ganglion neurons.

A new teleocidin analog was isolated from the fermentation medium of Streptomyces sp. MM216-87F4 and its structure was elucidated as 14-O-(N-acetylglucosaminyl) teleocidin A (GlcNAc-TA). GlcNAc-TA induces the translocation of protein kinases Calpha and theta fused with enhanced green fluorescent protein (PKCalpha-EGFP and PKCtheta-EGFP) to the plasma membrane in stable transfectants, and reduces intracellular calcium mobilization induced by agonists of G-protein coupled receptors in various cell lines without causing irritation of the mouse ear. Further, GlcNAc-TA sensitizes the release of excitatory neuropeptides substance P induced by capsaicin from primary-cultured dorsal root ganglion (DRG) neurons of the rat and GlcNAc-TA alone also triggers substance P release in a dose-dependent manner. This study provides the first observation that a teleocidin analog without a free hydroxyl group at C-14 acts as a PKC activator and directly induces the release of excitatory neuropeptide.