Contribution of Ca(2+) -dependent protein kinase C in the spinal cord to the development of mechanical allodynia in diabetic mice.
Contribution of Ca(2+) -dependent protein kinase C in the spinal cord to the development of mechanical allodynia in diabetic mice.
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DOI：
10.1248/bpb.30.990
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发表时间：
2007-05
影响因子：
2
通讯作者：
K. Honda;Masako Koguchi;K. Koga;Kyoko Nakajima;Fumito Kobayashi;K. Migita;S. Ogata;Y. Hirabara;Y. Takano
中科院分区：
文献类型：
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作者：
K. Honda;Masako Koguchi;K. Koga;Kyoko Nakajima;Fumito Kobayashi;K. Migita;S. Ogata;Y. Hirabara;Y. Takano
本文首次直接证明了糖尿病小鼠脊髓中钙依赖性蛋白激酶C（PKC）的激活。链脲佐菌素（STZ）处理（200 mg/kg，i. v.）糖尿病小鼠在注射STZ后7 d出现机械刺激超敏反应（异常性疼痛）。鞘内注射PKC抑制剂1-（5-异喹啉磺酰基）-2-甲基哌嗪（H-7）和calphostin C可抑制这种机械性异常性疼痛，但不能抑制蛋白激酶A抑制剂N-[2-（p-溴肉桂氨基）乙基]-5-异喹啉磺酰胺（H-89）。STZ诱导的糖尿病小鼠脊髓中膜相关的Ca（2+）依赖性PKC活性显著高于非糖尿病小鼠。这些结果表明，脊髓中Ca（2+）依赖性PKC的激活有助于糖尿病神经病变相关疼痛中的机械异常性疼痛。
In this paper, we directly demonstrate, for the first time, the activation of Ca(2+)-dependent protein kinase C (PKC) in the spinal cord of diabetic mice. In streptozotocin (STZ)-treated (200 mg/kg, i.v.) diabetic mice, hypersensitivity (allodynia) to mechanical stimulation appeared 7 d after STZ injection. This mechanical allodynia was inhibited by intrathecal injection of the PKC inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) and calphostin C, but not the protein kinase A inhibitor N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89). The activity of membrane-associated Ca(2+)-dependent PKC in the spinal cords of STZ-induced diabetic mice was significantly higher than that observed in non-diabetic mice. These results suggest that activation of Ca(2+)-dependent PKC in the spinal cord, contributes to the mechanical allodynia in the pain associated with diabetic neuropathy.