TRANSGENIC SUPEROXIDE-DISMUTASE MICE DIFFER IN OPIOID-INDUCED ANALGESIA
TRANSGENIC SUPEROXIDE-DISMUTASE MICE DIFFER IN OPIOID-INDUCED ANALGESIA
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DOI：
10.1016/0014-2999(95)00365-r
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发表时间：
1995-09-05
影响因子：
5
通讯作者：
CADET, JL
中科院分区：
文献类型：
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作者：
ELMER, GI;EVANS, JL;CADET, JL
携带人Cu/Zn-超氧化物歧化酶基因的转基因小鼠的放射自显影数据表明多巴胺能相关区域和中央灰色区域的μ阿片受体浓度增加。评估μ-、δ-和κ-阿片受体激动剂在杂合和纯合超氧化物歧化酶转基因小鼠以及4个近交系中诱导抗伤害感受的相对效力，以确定受体浓度增加的功能意义。增加的超氧化物歧化酶活性导致以基因剂量依赖性方式对μ激动剂的敏感性增加。SOD/Tg/hom小鼠对δ-激动剂的敏感性低于SOD/Tg/het小鼠。超氧化物歧化酶转基因不影响κ-阿片受体激动剂的敏感性。这些数据表明，δ-阿片受体的调节方式与μ-阿片受体不同，κ-阿片受体不受超氧化物歧化酶活性的影响。
Autoradiographic data from transgenic mice carrying the human Cu/Zn-superoxide dismutase gene demonstrate an increase in mu-opioid receptor concentration in dopaminergic-related areas and the central grey area. The relative potencies of mu-, delta- and kappa-opioid receptor agonists to induce antinociception in heterozygous and homozygous superoxide dismutase transgenic mice as well as four inbred strains were assessed to determine the functional significance of the increased receptor concentration. Increased superoxide dismutase activity results in an increased sensitivity to mu-agonists in a gene dosage-dependent manner. SOD/Tg/hom mice were less sensitive to the delta-agonist than were SOD/Tg/het mice. The superoxide dismutase transgene did not affect kappa-opioid receptor agonist sensitivity. These data suggest that delta-opioid receptors are not regulated in the same manner as mu-opioid receptors and that kappa-opioid receptors are unaffected by superoxide dismutase activity.