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

1 We recently demonstrated that intrathecal administration of prostaglandin E-2 (PGE(2)) and PGF(2 alpha) 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 curd slices by a chemiluminescence method. 2 PGE(2) stimulated NO release from both dorsal and ventral regions all along the spinal cord. PGE(2) stimulated the release within 10 min and increased it in a lime-dependent manner. 3 The PGE(2)-induced NO release was observed at 100 nM-10 mu M. PGF(2), stimulated the release at concentrations higher than 1 mu M, but PGD(2) (up to 10 mu M) did not enhance it. 4 17-Phenyl-omega-trinor PGE(2) (EP1 > EP3) and sulprostone (EP1 < EP3) were as patent as PGE(2), but PGE(1) was less potent, in stimulating NO release. While M&B 28767 (EP3) did not enhance the release, butaprost (EP2) stimulated it at 1 mu M. The PGE(2)-evoked release was blocked by ONO-NT-012, a bifunctional EP1 antagonist/EP3 agonist. 5 The PGE(2)-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 PGD(2) and dibutyryl-cyclic AMP. 6 The present study demonstrated that PGE(2) 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 PGE(2)-induced allodynia.