Malmberg A B, Yaksh T L
Department of Anesthesiology, University of California, San Diego, La Jolla, 92093.
Eur J Pharmacol. 1994 Dec 27;271(2-3):293-9. doi: 10.1016/0014-2999(94)90786-2.
The release of prostaglandin E2 was examined from superfused spinal cord slices. The addition of capsaicin to the perfusate resulted in a dose-dependent increase of prostaglandin E2-like immunoreactivity. Capsaicin (10 microM) evoked prostaglandin E2 release from basal levels of 5.3 +/- 0.8 to 30 +/- 3 fmol/10 min fraction. The capsaicin-evoked release was blocked by the capsaicin receptor antagonist capsazepine (10 microM), but not by removal of extracellular Ca2+ ions. Addition of non-steroidal anti-inflammatory drugs (NSAIDs) to the perfusate had no effect on resting levels of prostaglandin E2, but resulted in a concentration-dependent suppression of capsaicin-evoked release of prostaglandin E2. The IC50 values (in microM) were: indomethacin: 0.7, S(+)-flurbiprofen: 2.0, acetaminophen: 4.4,ketorolac: 5.0, R(-)-flurbiprofen: 8.7, S(+)-ibuprofen: 9.5, and for R(-)-ibuprofen: > 10. The relative potency for the NSAIDs to reduce capsaicin-evoked prostaglandin E2 release, with the exception of acetaminophen, corresponds to their antinociceptive activity after spinal delivery, a finding which further supports the role of prostanoids in spinal nociceptive processing.
对灌流的脊髓切片中前列腺素E2的释放进行了检测。向灌流液中添加辣椒素会导致前列腺素E2样免疫反应性呈剂量依赖性增加。辣椒素（10微摩尔）使前列腺素E2的释放从基础水平的5.3±0.8飞摩尔/10分钟馏分增加到30±3飞摩尔/10分钟馏分。辣椒素诱发的释放被辣椒素受体拮抗剂辣椒平（10微摩尔）阻断，但去除细胞外钙离子则无此作用。向灌流液中添加非甾体抗炎药（NSAIDs）对前列腺素E2的基础水平没有影响，但会导致辣椒素诱发的前列腺素E2释放呈浓度依赖性抑制。半数抑制浓度（IC50）值（以微摩尔计）分别为：吲哚美辛：0.7，S（+）-氟比洛芬：2.0，对乙酰氨基酚：4.4，酮咯酸：5.0，R（-）-氟比洛芬：8.7，S（+）-布洛芬：9.5，R（-）-布洛芬：>10。除对乙酰氨基酚外，NSAIDs降低辣椒素诱发的前列腺素E2释放的相对效力与其脊髓给药后的镇痛活性相对应，这一发现进一步支持了前列腺素在脊髓伤害性感受处理中的作用。
