Modification of K-opioid receptor agonist-induced antinociception by diabetes in the mouse brain and spinal cord
Modification of K-opioid receptor agonist-induced antinociception by diabetes in the mouse brain and spinal cord
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DOI：
10.1254/jphs.fp0040621
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发表时间：
2005-05-01
影响因子：
3.5
通讯作者：
Kamei, J
中科院分区：
文献类型：
--
作者：
Ohsawa, M;Kamei, J
在糖尿病和非糖尿病小鼠中，使用甩尾试验检查了几种K-阿片受体激动剂的脊髓上和脊髓抗伤害性感受作用。鞘内（i.t.）而不是脑室内（i. c. v.），CI-977是一种高选择性的κ（1）阿片受体激动剂，在糖尿病小鼠中的作用低于非糖尿病小鼠。ICI-199，441和R-84760，高效κ（1）-阿片受体激动剂，i. c. v.，但不是IT，与非糖尿病小鼠相比，糖尿病小鼠中的这些被减弱。另一方面，i. c. v.和i.t.糖尿病组小鼠的血清总胆固醇水平明显低于非糖尿病组。这些结果表明，这些K-阿片受体激动剂在糖尿病小鼠中的抗伤害性作用在中枢神经系统（CNS）中以区域特异性方式改变。糖尿病小鼠中x-阿片受体亚型的功能障碍可能是这些K-阿片受体激动剂作用的CNS区域特异性变化的基础。
The supraspinal and spinal antinociceptive effects of several K-Opioid receptor agonists were examined in diabetic and non-diabetic mice using the tail-flick assay. The antinociception induced by intrathecal (i.t.), but not intracerebroventricular (i.c.v.), CI-977, a highly selective kappa(1)-opioid receptor agonist, in diabetic mice was less than that in non-diabetic mice. The antinociceptive effects of ICI-199,441 and R-84760, high potency kappa(1)-opioid receptor agonists, given i.c.v., but not i.t., were attenuated in diabetic mice compared to those in nondiabetic mice. On the other hand, the antinociceptive effects of the new K-Opioid receptor agonist TRK-820, which has high affinity for kappa(2)- and/or kappa(3)-opioid receptors, injected both i.c.v. and i.t. in diabetic mice were markedly less than those in non-diabetic mice. These results indicate that the antinociceptive effects of those K-Opioid receptor agonists in diabetic mice are altered in a region-specific manner in the central nervous system (CNS). The dysfunction of x-opioid receptor subtypes in diabetic mice may underlie this CNS region-specific variation in the effects of these K-Opioid receptor agonists.