Kamei J, Iwamoto Y, Misawa M, Nagase H, Kasuya Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
Life Sci. 1994;55(6):PL121-6. doi: 10.1016/0024-3205(94)90062-0.
We assessed the effect of diabetes on antinociception produced by intracerebroventricular injection of delta-opioid receptor agonists [D-Pen2,5]enkephalin (DPDPE) and [D-Ala2]deltorphin II. The antinociceptive effect of DPDPE (10 nmol), administered i.c.v., was significantly greater in diabetic mice than in non-diabetic mice. The antinociceptive effect of i.c.v. DPDPE was significantly reduced in both diabetic and non-diabetic mice following pretreatment with 7-benzylidenenaltrexone (BNTX), a selective delta 1-opioid receptor antagonist, but not with naltriben (NTB), a selective delta 2-opioid receptor antagonist. There were no significant differences in the antinociceptive effect of [D-Ala2]deltorphin II (3 nmol, i.c.v.) in diabetic and non-diabetic mice. Furthermore, the antinociceptive effect of i.c.v. [D-Ala2]deltorphin II was significantly reduced in both diabetic and non-diabetic mice following pretreatment with NTB, but not with BNTX. In conclusion, mice with diabetes are selectively hyper-responsive to supraspinal delta 1-opioid receptor-mediated antinociception, but are normally responsive to activation of delta 2-opioid receptors.
我们评估了糖尿病对脑室内注射δ-阿片受体激动剂[D- Pen2,5]脑啡肽（DPDPE）和[D- Ala2]强啡肽II所产生的抗伤害感受作用的影响。脑室内注射10 nmol DPDPE后，糖尿病小鼠的抗伤害感受作用显著强于非糖尿病小鼠。在糖尿病和非糖尿病小鼠中，预先使用选择性δ1-阿片受体拮抗剂7-苄叉基纳曲酮（BNTX）预处理后，脑室内注射DPDPE的抗伤害感受作用均显著降低，但使用选择性δ2-阿片受体拮抗剂纳曲苄（NTB）预处理则无此效果。糖尿病和非糖尿病小鼠脑室内注射3 nmol [D- Ala2]强啡肽II后的抗伤害感受作用无显著差异。此外，在糖尿病和非糖尿病小鼠中，预先使用NTB预处理后，脑室内注射[D- Ala2]强啡肽II的抗伤害感受作用均显著降低，但使用BNTX预处理则无此效果。总之，糖尿病小鼠对脊髓上δ1-阿片受体介导的抗伤害感受作用具有选择性高反应性，但对δ2-阿片受体的激活反应正常。
