Stimulation of nitric oxide release from rat spinal cord by prostaglandin E₂

Abstract

1. We recently demonstrated that intrathecal administration of prostaglandin E₂ (PGE₂) and PGF_2α induced allodynia through a pathway that includes the glutamate receptor and nitric oxide (NO)-generating systems from pharmacological studies. In order to clarify the involvement of NO in prostaglandin-induced allodynia, we measured NO released from rat spinal cord slices by a chemiluminescence method.

2. PGE₂ stimulated NO release from both dorsal and ventral regions all along the spinal cord. PGE₂ stimulated the release within 10 min and increased it in a time-dependent manner.

3. The PGE₂-induced NO release was observed at 100 nM–10 μM. PGF_2α stimulated the release at concentrations higher than 1 μM, but PGD₂ (up to 10 μM) did not enhance it.

4. 17-Phenyl-ω-trinor PGE₂ (EP₁>EP₃) and sulprostone (EP₁<EP₃) were as potent as PGE₂, but PGE₁ was less potent, in stimulating NO release. While M&B 28767 (EP₃) did not enhance the release, butaprost (EP₂) stimulated it at 1 μM. The PGE₂-evoked release was blocked by ONO-NT-012, a bifunctional EP₁ antagonist/EP₃ agonist.

5. The PGE₂-evoked release was Ca²⁺-dependent and blocked by MK-801 (NMDA receptor antagonist) and L-NAME (NO synthase inhibitor). The release was also inhibited by PGD₂ and dibutyryl-cyclic AMP.

6. The present study demonstrated that PGE₂ stimulates NO release in the rat spinal cord by activation of NMDA receptors through the EP₁ receptor, and supports our previous findings that the NO-generating system is involved in the PGE₂-induced allodynia.

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