Stereoselective effect of morphine on antinociception and endogenous opioid peptide levels in plasma but not cerebrospinal fluid of dogs.
Stereoselective effect of morphine on antinociception and endogenous opioid peptide levels in plasma but not cerebrospinal fluid of dogs.
复制标题
吗啡对狗血浆中而非脑脊液中的镇痛和内源性阿片肽水平的立体选择性作用。
DOI：
10.1016/0024-3205(91)90039-e
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发表时间：
1991
期刊：
影响因子：
6.1
通讯作者：
Dewey,WL
中科院分区：
文献类型：
--
作者：
Adams,ML;Morris,DL;Brase,DA;Dewey,WL
吗啡释放内源性阿片类物质进入狗的循环。为了测试这种作用的立体特异性，以及确定吗啡是否也集中释放内源性阿片样物质，这可能涉及其抗伤害作用，（10 mg/kg，sc）或（+）-吗啡氢溴酸盐对狗甩尾试验中的抗伤害感受，对半定量吗啡诱导的流涎、呕吐、排便和共济失调体征，并研究了对血浆和脑脊液（CSF）内源性阿片肽水平的影响。通过放射免疫测定法定量十八烷基硅基硅胶柱提取物中免疫反应性β-内啡肽（i-BE）、甲硫脑啡肽（i-ME）、亮脑啡肽（i-LE）和强啡肽（i-DY）的血浆和CSF水平。在未提取的样品中测量免疫反应性吗啡（i-M）水平。（−）-吗啡处理显著增加抗伤害感受、吗啡诱导的体征、血浆和CSF中的i-M水平以及血浆中的i-BE、i-ME和i-LE水平，但不增加CSF。i-DY水平在血浆和CSF中保持恒定。（+）-吗啡处理没有改变任何这些参数，表明吗啡对犬的伤害感受、行为体征和血浆内源性阿片类药物的影响具有立体选择性。它的结论是，吗啡不会导致增加免疫反应性内源性阿片肽在CSF中的时间，其峰值抗伤害效应。
Morphine releases endogenous opioids into the circulation of dogs. To test the stereospecificity of this effect, as well as to determine whether morphine also releases endogenous opioids centrally, which might be involved in its antinociceptive action, the effects of (−)-morphine sulfate (10 mg/kg, sc) or (+)-morphine hydrobromide on antinociception in a dog tail-flick test, on semi-quantified morphine-induced signs of salivation, emesis, defecation and ataxia, and on the plasma and cerebrospinal fluid (CSF) levels of endogenous opioid peptides were studied. Plasma and CSF levels of immunoreactive β-endorphin (i-BE), met-enkephalin (i-ME), leu-enkephalin (i-LE), and dynorphin (i-DY) were quantified by radioimmunoassay in octadecylsilyl-silica cartridge extracts. Immunoreactive morphine (i-M) levels were measured in unextracted samples. (−)-Morphine treatment significantly increased antinociception, morphine-induced signs, i-M levels in plasma and CSF, and i-BE, i-ME, and i-LE levels in plasma, but not CSF. Levels of i-DY remained constant in plasma and CSF. (+)-Morphine treatment did not alter any of these parameters, indicating that the effects of morphine on nociception, behavioral signs, and plasma endogenous opioids in dogs were stereoselective. It is concluded that morphine does not cause an increase in immunoreactive endogenous opioid peptides in the CSF at the time of its peak antinociceptive effect.