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.
Microbial Chemistry Research Center, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan. nakaek@bikaken.or.jp
Koichi
K
Nakae
Nobuo
N
Hosokawa
Ryuichi
R
Sawa
Yumiko
Y
Kubota
Tohru
T
Masuda
Syunichi
S
Ohba
Masayuki
M
Igarashi
Naoko
N
Nakagawa
Yoshio
Y
Nishimura
Yuzuru
Y
Akamatsu
D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006224:Cricetinae; D005260:Female; D005285:Fermentation; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007509:Irritants / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D008235:Lyngbya Toxins / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008813:Mice, Inbred ICR; D018613:Microscopy, Confocal; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007509:Irritants; D007527:Isoenzymes; D008235:Lyngbya Toxins; C022176:teleocidins; D013373:Substance P; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002211:Capsaicin; D002118:Calcium