Morphine tolerance increases [3H]MK‐801 binding affinity and constitutive neuronal nitric oxide synthase expression in rat spinal cord
Morphine tolerance increases [3H]MK‐801 binding affinity and constitutive neuronal nitric oxide synthase expression in rat spinal cord
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DOI：
10.1093/bja/85.4.587
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发表时间：
2000-10
期刊：
影响因子：
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通讯作者：
Chih-Shung Wong;M. Hsu;Y. Chou;P. Tao;C. Tung
中科院分区：
文献类型：
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作者：
Chih-Shung Wong;M. Hsu;Y. Chou;P. Tao;C. Tung
N -甲基-d-天冬氨酸（NMDA）受体拮抗剂和一氧化氮合酶（NOS）抑制剂抑制吗啡耐受。在本研究中，腰椎蛛网膜下腔聚乙烯（PE 10）导管植入给药，以研究在吗啡耐受大鼠脊髓模型中NMDA受体活性和NOS蛋白表达的变化。鞘内（i.t.）吗啡输注（10 μg h-1）5天。联合给予（+）-5-甲基-10，11-二氢-5 H -二苯并[ a，d ]环庚烯-5，10-亚胺马来酸盐（MK-801）（10 μg h −1 i.t.）与吗啡联合应用，以抑制吗啡耐受的发展。取腰段脊髓，制备[ 3 H]MK-801结合试验和NOS蛋白质印迹法。吗啡耐受大鼠脊髓中[ 3 H]MK-801的结合亲和力（平均（sem）KD =0.41（0.09）nM）高于对照大鼠（1.50（0.13）nM）。B max无差异。Western blot分析显示吗啡耐受组神经元型NOS（nNOS）蛋白的组成性表达是对照组的2倍。这种上调部分被MK-801阻止。结果表明，吗啡耐受影响大鼠脊髓NMDA受体结合活性，增加nNOS表达。
N -Methyl-d-aspartate (NMDA) receptor antagonists and nitric oxide synthase (NOS) inhibitors inhibit morphine tolerance. In the present study, a lumbar subarachnoid polyethylene (PE 10 ) catheter was implanted for drug administration to study alterations in NMDA receptor activity and NOS protein expression in a morphine-tolerant rat spinal model. Antinociceptive tolerance was induced by intrathecal (i.t.) morphine infusion (10 μg h −1 ) for 5 days. Co-administered (+)-5-methyl-10,11-dihydro- 5 H -dibenzo[ a , d ]cyclohepten-5,10-imine maleate (MK-801) (10 μg h −1 i.t.) with morphine was used to inhibit the development of morphine tolerance. Lumbar spinal cord segments were removed and prepared for [ 3 H]MK-801 binding assays and NOS western blotting. The binding affinity of [ 3 H]MK-801 was higher in spinal cords of morphine-tolerant rats (mean (sem) K D =0.41 (0.09) nM) than in control rats (1.50 (0.13) nM). There was no difference in B max . Western blot analysis showed that constitutive expression of neuronal NOS (nNOS) protein in the morphine-tolerant group was twice that in the control group. This up-regulation was partially prevented by MK-801. The results suggest that morphine tolerance affects NMDA receptor binding activity and increases nNOS expression in the rat spinal cord.