Prostaglandin E(2) enhances axonal transport and neuritogenesis in cultured mouse dorsal root ganglion neurons.
The effects of prostaglandin E(2) on axonal transport in cultured mouse dorsal root ganglion neurons were investigated by analysing the number of axonally transported particles under video-enhanced microscopy. Application of prostaglandin E(2) increased the number of particles transported in anterograde and retrograde directions. The EP(2) prostaglandin receptor agonist butaprost mimicked the effect of prostaglandin E(2), but the EP(1)/EP(3) prostaglandin receptor agonist 17-phenyl trinor prostaglandin E(2) and the EP(3) prostaglandin receptor agonist M&B 28767 had no effect. The membrane-permeable cyclic AMP analogue dibutyryl cyclic AMP and the adenylate cyclase activator forskolin mimicked the effect of prostaglandin E(2). The protein kinase A inhibitor H-89 reversibly reduced the number of particles in both anterograde and retrograde directions. The effects of prostaglandin E(2) and dibutyryl cyclic AMP were blocked by H-89. Taken together with previous biochemical studies showing that prostaglandin E(2) increases cyclic AMP levels, the present results suggest that prostaglandin E(2) enhances axonal transport via the EP(2) receptor and cyclic AMP-dependent protein kinase A pathway. We further investigated the role of prostaglandin E(2) in neurite growth. Prostaglandin E(2) increased both the number of cells exhibiting neurites and the neurite growth rate, operating by a similar mechanism to stimulation of axonal transport. Prostaglandin E(2) may modulate axonal transport to supply materials for morphogenesis as well as other functions in sensory neurons.
Hiruma
H
H
Department of Physiology, Kitasato University School of Medicine, 1-15-1 Kitasato, 228-8555, Sagamihara, Japan. hiruma@med.kitasato-u.ac.jp
Ichikawa
T
T
Kobayashi
H
H
Hoka
S
S
Takenaka
T
T
Kawakami
T
T
D000818:Animals; D001370:Axonal Transport; D002478:Cells, Cultured; D015232:Dinoprostone / Q000819:agonists / Q000494:pharmacology / Q000502:physiology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000648:ultrastructure*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016501:Neurites / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction; D014741:Video Recording
D015232:Dinoprostone