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Differential effects of wortmannin on the release of substance P and amino acids from the isolated spinal cord of the neonatal rat
Author(s) -
Suzuki Hidenori,
Yoshioka Koichi,
Maehara Taketoshi,
Guo JiangZhong,
omura Yoshiaki,
Otsuka Masanori
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702243
Subject(s) - wortmannin , spinal cord , dorsal root ganglion , substance p , glutamate receptor , depolarization , myosin light chain kinase , stimulation , chemistry , endocrinology , medicine , anatomy , biology , neuroscience , biochemistry , neuropeptide , myosin , kinase , phosphatidylinositol , receptor
Effects of wortmannin, an inhibitor of myosin light chain kinase, on the release of substance P and amino acids, GABA and glutamate, were investigated in the isolated spinal cord preparation of the neonatal rat. Wortmannin at 0.5–10 μ M depressed the release of substance P evoked by high‐K+ (90 m M ) medium from the spinal cord (IC 50 =1.1 μ M ). Wortmannin also depressed the high‐K+ (70 m M )‐evoked release of substance P from cultured dorsal root ganglion neurons of neonatal rats. In contrast, the high‐K+ (90 m M )‐evoked release of GABA and glutamate from the spinal cord was not affected by wortmannin (0.1–10 μ M ). Upon stimulation of a dorsal root, a monosynaptic reflex and a subsequent slow ventral root depolarization were evoked in the ipsilateral ventral root of the same segment in the isolated spinal cord preparation. The magnitude of the slow ventral root depolarization was depressed gradually to about 70% of the control during the course of 30 min under wortmannin (1 μ M ). In contrast, the monosynaptic reflex was unaffected by wortmannin. Immunofluorescent staining revealed that immunoreactivities of substance P and myosin II were colocalized at presynaptic terminals in the dorsal horn of the neonatal rat spinal cord. The present results suggest that myosin phosphorylation by myosin light chain kinase may play a crucial role in the release of substance P, but not in the release of GABA and glutamate in the neonatal rat spinal cord. This may reflect a difference in the exocytic mechanisms of substance P‐containing large dense core vesicles and amino acid‐containing small clear vesicles.