Prostaglandin E 2 enhances axonal transport and neuritogenesis in cultured mouse dorsal root ganglion neurons

Abstract

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.