Stimulation of nitric oxide release from rat spinal cord by prostaglandin E2.
1. We recently demonstrated that intrathecal administration of prostaglandin E2 (PGE2) and PGF2alpha 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 microM. PGF2alpha stimulated the release at concentrations higher than 1 microM, but PGD2 (up to 10 microM) did not enhance it. 4. 17-Phenyl-omega-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 microM. 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.
Sakai
M
M
Department of Anesthesiology, Osaka Medical College, Takatsuki, Japan.
Minami
T
T
Hara
N
N
Nishihara
I
I
Kitade
H
H
Kamiyama
Y
Y
Okuda
K
K
Takahashi
H
H
Mori
H
H
Ito
S
S
D000818:Animals; D015232:Dinoprostone / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018078:Receptors, Prostaglandin E / Q000819:agonists; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
D018078:Receptors, Prostaglandin E; D009569:Nitric Oxide; D015232:Dinoprostone