Morphine induces apoptosis in murine thymocytes in vivo but not in vitro: involvement of both opiate and glucocorticoid receptors.
Morphine induces apoptosis in murine thymocytes in vivo but not in vitro: involvement of both opiate and glucocorticoid receptors.
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发表时间：
1993-07
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通讯作者：
B. Fuchs;S. Pruett
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作者：
B. Fuchs;S. Pruett
我们验证了一种假设，即先前观察到的小鼠胸腺淋巴细胞在缓释吗啡颗粒治疗后的丢失是通过细胞凋亡的过程发生的。细胞凋亡是细胞死亡的一种形式，与坏死不同，坏死涉及一种特定的内切酶，它会使细胞自身的DNA碎裂。在B6C3F1小鼠体内植入缓释吗啡颗粒48小时后，胸腺重量和细胞密度减少到安慰剂组的30%。研究发现，注射吗啡颗粒的小鼠胸腺细胞的DNA片段百分率明显高于植入安慰剂颗粒的小鼠胸腺细胞或幼稚对照小鼠的胸腺细胞。DNA片段化的高峰出现在颗粒植入后大约12小时。当在琼脂糖凝胶上分离时，观察到的DNA片段的大小相当于180个碱基对的倍数，这是细胞凋亡的特征。在体内，阿片受体拮抗剂纳洛酮或糖皮质激素受体拮抗剂RU-38486均能完全阻断吗啡诱导的胸腺细胞凋亡的增加。在体外实验中，胸腺细胞在吗啡浓度高达10(-4)M的情况下培养，没有证据表明DNA断裂率增加。这些数据表明阿片受体和糖皮质激素受体都参与了吗啡诱导的细胞凋亡，而阿片受体并不位于胸腺淋巴细胞上。
We tested the hypothesis that the previously observed loss of thymic lymphocytes in mice after treatment with time-release morphine pellets was occurring through the process of apoptosis. Apoptosis is a form of cell death, distinct from necrosis, which involves a specific endonuclease that fragments the cell's own DNA. Forty-eight hours after implantation of a time-release morphine pellet in B6C3F1 mice, thymus weight and cellularity was reduced to 30% of that observed in placebo-treated mice. Thymocytes from morphine pellet-treated mice were found to have a significantly greater percentage of their DNA fragmented than did thymocytes from either placebo pellet-implanted or naive control mice. The peak level of DNA fragmentation was found to occur approximately 12 hr postpellet implant. When separated on agarose gels, the sizes of the DNA fragments observed corresponded to the multiples of 180 base pairs which are characteristic of apoptosis. In vivo, the use of either the opiate receptor antagonist naloxone, or the glucocorticoid receptor antagonist RU-38486, was able to block completely the morphine mediated increase in thymocyte apoptosis. In vitro experiments in which thymocytes were cultured with morphine concentrations as high as 10(-4) M showed no evidence of an increased rate of DNA fragmentation. These data indicate that both opiate and glucocorticoid receptors are involved in morphine-induced apoptosis and that the opiate receptor responsible is not located on the thymic lymphocytes.