Zaltoprofen Inhibits Bradykinin-Mediated Enhancement of Glutamate Receptor Activity in Substantia Gelatinosa Neurons
Zaltoprofen Inhibits Bradykinin-Mediated Enhancement of Glutamate Receptor Activity in Substantia Gelatinosa Neurons
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DOI：
10.1213/ane.0b013e31821c693c
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发表时间：
2011-08
影响因子：
5.7
通讯作者：
T. Kohno
中科院分区：
文献类型：
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作者：
T. Kohno
背景：Zaltoprofen是一种非甾体抗炎药的丙酸衍生物，被认为可以抑制缓激肽介导的伤害感受。在这里，我试图阐明zaltoprofen对缓激肽介导的脊髓浅表背角兴奋性谷氨酸能传递增强的阻断作用的分子机制。方法：采用全细胞膜片钳技术，观察zaltoprofen对外源性-氨基-3-羟基-5-甲基-4-异恶唑-4-丙酸（AMPA）电流对成年大鼠脊髓切片II层神经元反应的影响。结果：缓行激肽（10 M）预处理后，AMPA电流明显增强。然而，zaltoprofen （1,10 M）和非选择性环氧化酶(COX)-1和COX-2抑制剂布洛芬阻断了缓激肽介导的增强作用。加入前列腺素E2可以消除布洛芬的抑制作用，而不影响扎尔托洛芬的抑制作用。此外，在蛋白激酶C （PKC）激活剂存在的情况下，zaltoprofen的抑制作用被消除，而在磷脂酶C激活剂存在的情况下，zaltoprofen的作用仍然存在。结论：上述结果提示，zaltoprofen的抗痛觉作用可能通过抑制蛋白激酶C激活来阻断缓激肽对AMPA电流的增强作用，而不影响浅表背角的COX。
BACKGROUND: Zaltoprofen, a propionic acid derivative of nonsteroidal anti-inflammatory drugs, has been proposed to inhibit the nociception mediated by bradykinin. Here, I attempted to clarify the molecular mechanisms underlying the blocking effect of zaltoprofen on bradykinin-mediated enhancement of excitatory glutamatergic transmission in the superficial dorsal horn of the spinal cord. METHODS: The effects of zaltoprofen on the response to exogenous administration of -amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid (AMPA) currents were examined in lamina II neurons of adult rat spinal cord slices using the whole-cell patch-clamp technique. RESULTS: AMPA currents were significantly enhanced by preapplication of bradykinin (10 M). However, zaltoprofen (1, 10 M) and a nonselective cyclooxygenase (COX)-1 and COX-2 inhibitor, ibuprofen, blocked the bradykinin-mediated enhancing effect. The inhibitory effect of ibuprofen, but not zaltoprofen, was removed by adding prostaglandin E2. Furthermore, the inhibitory effect of zaltoprofen was removed in the presence of protein kinase C (PKC) activator, whereas the effect of zaltoprofen was still present in the presence of phospholipase C activator. CONCLUSIONS: These findings suggest that the antinociceptive effect of zaltoprofen may block the augmenting effect of bradykinin on AMPA currents through inhibition of protein kinase C activation, without affecting COX in the superficial dorsal horn.