Antagonism of phosphoramidon-induced antinociception in mice by mu- but not kappa-opioid receptor blockers.
Antagonism of phosphoramidon-induced antinociception in mice by mu- but not kappa-opioid receptor blockers.
复制标题
mu-而非kappa-阿片受体阻滞剂对小鼠中磷酰胺诱导的镇痛作用有拮抗作用。
DOI：
10.1016/j.lfs.2007.02.019
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发表时间：
2007
期刊：
影响因子：
6.1
通讯作者：
Quock,RaymondM
中科院分区：
文献类型：
--
作者：
Pruhs,RonaldJ;Peña,RoehlT;Quock,RaymondM
脑室内（i. c. v.）中性内肽酶24.11-抑制剂phosphoramidon的给药在小鼠乙酸腹部收缩试验中引起剂量依赖性抗伤害感受作用。本研究的目的是确定阿片受体亚型介导的磷酰胺抗伤害在这个范例。在用phosphoramidon，i. c. v.，μ-阿片激动剂舒芬太尼，皮下注射，或κ-阿片激动剂U-50，488 H，s.c.纳洛酮在i. c. v.剂量下显著减弱磷酰胺诱导的抗伤害感受，该剂量也阻断舒芬太尼和U-50，488 H。μ-阿片受体拮抗剂β-FNA（β-FNA）在i. c. v.剂量下可阻断phosphoramidon和舒芬太尼，但不能阻断U-50，488 H。κ-阿片受体拮抗剂nor-binaltorphimine（nor-BNI）产生剂量相关效应。低剂量（10 μg）的nor-BNI对phosphoramidon或舒芬太尼没有影响，但确实降低了U-50，488 H的抗伤害作用。较高剂量（30 μg）的nor-BNI阻断了phosphoramidon、舒芬太尼和U-50，488 H，表明在该剂量下κ-阿片受体选择性丧失。这些结果表明，μ-而不是κ-阿片受体介导的磷酰胺诱导的抗伤害性在腹部收缩试验。
Intracerebroventricular (i.c.v.) administration of the neutral endopeptidase 24.11-inhibitor phosphoramidon evoked a dose-dependent antinociceptive effect in the mouse acetic acid abdominal constriction test. The present study was conducted to identify the opioid receptor subtype(s) that mediate phosphoramidon antinociception in this paradigm. Mice were pretreated with different opioid antagonists prior to being challenged with phosphoramidon, i.c.v., the μ-opioid agonist sufentanil, s.c., or the κ-opioid agonist U-50,488H, s.c. Naltrexone significantly attenuated phosphoramidon-induced antinociception at an i.c.v. dose that also blocked both sufentanil and U-50,488H. The μ-opioid antagonist β-funaltrexamine (β-FNA) blocked phosphoramidon and sufentanil at an i.c.v. dose that did not block U-50,488H. The κ-opioid antagonist nor-binaltorphimine (nor-BNI) produced dose-related effects. A low dose (10 μg) of nor-BNI had no effect on either phosphoramidon or sufentanil but did reduce U-50,488H antinociception. A higher dose (30 μg) of nor-BNI blocked phosphoramidon, sufentanil, and U-50,488H, suggesting a loss of κ-opioid receptor selectivity at this dose. These findings suggest that μ- but not κ-opioid receptors mediate phosphoramidon-induced antinociception in the abdominal constriction test.