Morphine-induced opioid receptor down-regulation detected in intact adult rat brain cells.

Morphine-induced opioid receptor down-regulation detected in intact adult rat brain cells.
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在完整的成年大鼠脑细胞中检测到吗啡诱导的阿片受体下调。

DOI:
10.1016/0014-2999(86)90223-2
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发表时间:
1986
影响因子:
5
通讯作者:
el-Fakahany,E
el-Fakahany,E
中科院分区:
医学2区
文献类型:
--
作者:
Rogers,NF;el-Fakahany,E

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利用成年大鼠脑分离的完整脑细胞,研究慢性吗啡在体内对阿片受体的调节作用。当比较假手术大鼠细胞与4个(2 × 2) 75 mg吗啡小丸治疗6天的大鼠细胞中[3H]纳洛酮在生理等渗透缓冲液中的特异性结合时,发现吗啡治疗导致[3H]纳洛酮结合位点密度显著降低。这种受体下调并不伴随着受体对配体亲和力的改变。在诱导耐受18小时后,吗啡的这种作用被逆转。当使用在相同生理缓冲液中制备和分析的脑匀浆进行类似实验时,与对照组相比,吗啡处理动物的[3H]纳洛酮结合位点数量增加。另一方面,在50 mM Tris-HCl缓冲液中进行结合实验时,对照组和吗啡处理组之间的配体结合没有明显差异。本研究结果表明,在完整的脑细胞中,慢性吗啡治疗对阿片受体有下调作用,并提示当使用其他组织制剂来评估受体密度时可能会得出不同的结论。
Intact brain cells dissociated from the brains of adult rats were used to study the regulation of opioid receptors by in vivo chronic morphine treatment. When the specific binding of [3H]naloxone in a physiological iso-osmotic buffer was compared in cells obtained from sham-operated rats and in those treated for 6 days with four (2 × 2) 75 mg morphine pellets, it was found that morphine treatment resulted in a significant reduction in the density of [3H]naloxone binding sites. This receptor down-regulation was not accompanied by a change in the receptor affinity for the ligand. This effect of morphine was reversed upon the removal of morphine pellets for 18 h after tolerance induction. When similar experiments were performed using brain homogenates prepared and assayed in the same physiological buffer, there was an increase in the number of [3H]naloxone binding sites in morphine-treated animals compared to controls. On the other hand, when the binding experiments were conducted in 50 mM Tris-HCl buffer, no difference in ligand binding was apparent between control and morphine-treated groups. The present results demonstrate opioid receptor down-regulation by chronic morphine treatment measured in intact brain cells, and suggest that different conclusions may be reached when other tissue preparations are used to assess the receptor density.
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