Chronic opioid antagonist treatment: assessment of receptor upregulation.
Chronic opioid antagonist treatment: assessment of receptor upregulation.
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慢性阿片拮抗剂治疗：受体上调评估。
DOI：
10.1016/0014-2999(89)90539-6
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发表时间：
1989
影响因子：
5
通讯作者：
Lutfy,K
中科院分区：
文献类型：
--
作者：
Yoburn,BC;Sierra,V;Lutfy,K
在接受阿片类拮抗剂纳曲酮（皮下植入颗粒）治疗 8 天的小鼠中，测定了特定脑阿片类药物结合和阿片类药物药效学的变化。长期阿片拮抗剂治疗增加了 [3H]纳洛酮 (+55%) 和 [3H][D-Ala2,D-Leu5]脑啡肽 (+41%) 的结合位点数量（上调），但没有改变配体的亲和力，如饱和研究中所确定的。吗啡对[3H]纳洛酮的置换研究也表明吗啡的亲和力没有变化。纳洛酮亲和力 (pA2) 的体内估计与体外结果一致，表明长期纳曲酮治疗不会改变纳洛酮亲和力。长期纳曲酮治疗（0.5、1.0、15.0 mg 丸剂）以剂量依赖性方式增加吗啡的镇痛效力（超敏性），相对效力最大增加为 1.8。然而，在仍植入纳曲酮颗粒的小鼠中进行测试，15 mg 纳曲酮颗粒能够将吗啡镇痛的剂量反应函数改变超过 300 倍。最低剂量的纳曲酮丸剂（0.5 mg）产生显着的吗啡镇痛拮抗作用，但没有产生显着的超敏反应。因此，超敏性和上调与阿片类药物作用的拮抗程度不成正比；小鼠的超敏感性与结合位点的增加有关，而不是通过体内和体外方法测定的受体亲和力的变化有关。
Changes in specific brain opioid binding and opioid pharmacodynamics were determined in mice treated with the opioid antagonist naltrexone (subcutaneously implanted pellets) for 8 days. Chronic opioid antagonist treatment increased the number of binding sites (upregulation) for [3H]naloxone (+55%) and [3H][D-Ala2,D-Leu5]enkephalin (+41%) but did not alter the affinity of the ligands, as determined in saturation studies. Displacement studies of [3H]naloxone by morphine also indicated that there was no change in morphine's affinity. In vivo estimation of naloxone affinity (pA2), agreed with the in vitro results indicating that chronic naltrexone treatment did not alter naloxone affinity. Chronic naltrexone treatment (0.5, 1.0, 15.0 mg pellets) increased the analgesic potency of morphine (supersensitivity) in a dose-dependent manner, up to a maximal increase in relative potency of 1.8. However, in mice tested with the naltrexone pellets still implanted, the 15 mg naltrexone pellet was able to shift the dose-response function for morphine analgesia more than 300-fold. The lowest dose naltrexone pellet (0.5 mg), produced significant antagonism of morphine analgesia, but did not produce significant supersensitivity. Thus, supersensitivity and upregulation are not proportional to the degree of antagonism of opioid effects; and supersensitivity in the mouse is related to increased binding sites and not to changes in receptor affinity as determined by in vivo and in vitro methods.
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μ-阿片受体在自由活动的大鼠中介导中脑“刺激产生的镇痛”的证据
影响因子：
3.3
作者：
M. Millan;A. Czzonkowski;A. Herz
通讯作者：
A. Herz
影响因子：
6.1
作者：
N. Brunello;A. Volterra;A. D. Di Giulio;V. Cuomo;G. Racagni
通讯作者：
N. Brunello;A. Volterra;A. D. Di Giulio;V. Cuomo;G. Racagni
蛋白质修饰试剂对阿片激动剂和拮抗剂受体结合的不同影响。
影响因子：
3.6
作者：
G. Pasternak;H. A. Wilson;S. Snyder
通讯作者：
S. Snyder
3H-纳洛酮在小鼠大脑中的结合：离子的影响和耐受性的发展。
DOI：
--
发表时间：
1974
期刊：
Life Science
影响因子：
--
作者：
Robert Hitzemann;Barbara A. Hitzemann;Horace H. Loh
通讯作者：
Horace H. Loh
影响因子：
6.1
作者：
T. Wolfle;J. Liebeskind
通讯作者：
J. Liebeskind