Prostaglandin E2 facilitates neurite outgrowth in a motor neuron-like cell line, NSC-34

J Pharmacol Sci. 2017 Oct;135(2):64-71. doi: 10.1016/j.jphs.2017.09.001. Epub 2017 Sep 8.


Prostaglandin E2 (PGE2) exerts various biological effects by binding to E-prostanoid receptors (EP1-4). Although recent studies have shown that PGE2 induces cell differentiation in some neuronal cells such as mouse DRG neurons and sensory neuron-like ND7/23 cells, it is unclear whether PGE2 plays a role in differentiation of motor neurons. In the present study, we investigated the mechanism of PGE2-induced differentiation of motor neurons using NSC-34, a mouse motor neuron-like cell line. Exposure of undifferentiated NSC-34 cells to PGE2 and butaprost, an EP2-selective agonist, resulted in a reduction of MTT reduction activity without increase the number of propidium iodide-positive cells and in an increase in the number of neurite-bearing cells. Sulprostone, an EP1/3 agonist, also significantly lowered MTT reduction activity by 20%; however, no increase in the number of neurite-bearing cells was observed within the concentration range tested. PGE2-induced neurite outgrowth was attenuated significantly in the presence of PF-0441848, an EP2-selective antagonist. Treatment of these cells with dibutyryl-cAMP increased the number of neurite-bearing cells with no effect on cell proliferation. These results suggest that PGE2 promotes neurite outgrowth and suppresses cell proliferation by activating the EP2 subtype, and that the cAMP-signaling pathway is involved in PGE2-induced differentiation of NSC-34 cells.

Keywords: E-prostanoid receptors; Motor neuron; Neurite outgrowth; Prostaglandin E2; cAMP.

MeSH terms

  • Alprostadil / analogs & derivatives
  • Alprostadil / pharmacology
  • Animals
  • Bucladesine / pharmacology
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Cyclic AMP / physiology
  • Dinoprostone / analogs & derivatives
  • Dinoprostone / metabolism
  • Dinoprostone / pharmacology*
  • Dinoprostone / physiology*
  • Mice
  • Motor Neurons / cytology*
  • Neurites / physiology*
  • Neuronal Outgrowth / drug effects*
  • Neuronal Outgrowth / genetics*
  • Receptors, Prostaglandin E / metabolism
  • Receptors, Prostaglandin E, EP2 Subtype / agonists
  • Receptors, Prostaglandin E, EP3 Subtype / agonists
  • Signal Transduction / physiology


  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP2 Subtype
  • Receptors, Prostaglandin E, EP3 Subtype
  • sulprostone
  • Bucladesine
  • Cyclic AMP
  • Alprostadil
  • butaprost
  • Dinoprostone