PERIPHERAL KAPPA-OPIOID RECEPTORS MEDIATE THE ANTINOCICEPTIVE EFFECT OF FETODOZINE ON THE DUODENAL PAIN REFLEX IN RAT
PERIPHERAL KAPPA-OPIOID RECEPTORS MEDIATE THE ANTINOCICEPTIVE EFFECT OF FETODOZINE ON THE DUODENAL PAIN REFLEX IN RAT
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DOI：
10.1016/0014-2999(94)90265-8
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发表时间：
1994-12-12
影响因子：
5
通讯作者：
JUNIEN, JL
中科院分区：
文献类型：
--
作者：
DIOP, L;RIVIERE, PJM;JUNIEN, JL
已证明非多托嗪通过外周κ阿片受体对胃肠道敏感性起作用。本研究探讨了非多托嗪和参比化合物吗啡和（+/-）-U-50，488 H对麻醉大鼠十二指肠疼痛的作用。伤害性刺激由十二指肠扩张（100 mm Hg; 30 s）产生。非多托嗪（1-5 mg/kg i. v.）对十二指肠扩张诱导的心血管反射产生剂量依赖性抑制（艾德（50）= 1.87 mg/kg），但在剂量高达300 μ g/大鼠时，或鞘内途径（i.t.）。μ阿片受体激动剂吗啡通过静脉注射（艾德（50）= 0.62 mg/kg）和静脉注射（艾德（50）= 2.17 μ g/大鼠）途径均具有活性，κ阿片受体激动剂（+/-）-U-50，488 H也是如此（反式-（+/-）-3，4-二氯-N-甲基-N-（2-[ 1-吡咯烷基]环己基）B苯乙酰胺）（静脉注射和静脉注射途径的艾德（50）分别为0.25 mg/kg和149 μ g/大鼠）。选择性κ-阿片受体拮抗剂，去甲-binaltorphimine（10 mg/kg s.c.），消除了对非多托嗪（5 mg/kg i. v.）和（+/-）-U-50，488H（2mg/kg i.v.）而对吗啡（1 mg/kg i. v.）则无此作用。相比之下，纳洛酮（30 μ g/kg i. v.）阻断对吗啡（lmg/kg i. v.）而非多托嗪（5 mg/kg i. v.）或（+/-）-U-50，488H（2mg/kg i.v.）。结论：非多托嗪对十二指肠疼痛的镇痛作用是通过外周κ阿片受体介导的。
Fedotozine has been shown to act on gastrointestinal sensitivity through peripheral kappa-opioid receptors. The present study investigated the action of fedotozine and reference compounds, morphine and (+/-)-U-50,488H, on duodenal pain in anesthetized rats. The noxious stimulus was produced by duodenal distension (100 mm Hg; 30 s). Fedotozine (1-5 mg/kg i.v.) produced a dose-dependent inhibition of the cardiovascular reflex induced by duodenal distension (ED(50) = 1.87 mg/kg) but had no effect at doses up to 300 mu g/rat by either intracerebroventricular (i.c.v.) or intrathecal routes (i.t.). The mu-opioid receptor agonist, morphine, was active by both i.v. (ED(50) = 0.62 mg/kg) and i.c.v. routes (ED(50) = 2.17 mu g/rat) as was the kappa-opioid receptor agonist, (+/-)-U-50,488H (trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[ 1-pyrrolidinyy]cyclohexyl)b enzeneacetamide) (ED(50) = 0.25 mg/kg and 149 mu g/rat for i.v. and i.c.v. routes, respectively). The selective kappa-opioid receptor antagonist, nor-binaltorphimine (10 mg/kg s.c.), abolished the response to fedotozine (5 mg/kg i.v.) and (+/-)-U-50,488H (2 mg/kg i.v.) but not that to morphine (1 mg/kg i.v.). In contrast, naloxone (30 mu g/kg i.v.) blocked the response to morphine (1 mg/kg i.v.) but not that to fedotozine (5 mg/kg i.v.) or (+/-)-U-50,488H (2 mg/kg i.v.). It is concluded that the antinociceptive effects of fedotozine on duodenal pain are mediated by peripheral kappa-opioid receptors.