Loss of SUR1 subtype KATP channels alters antinociception and locomotor activity after opioid administration.
Loss of SUR1 subtype KATP channels alters antinociception and locomotor activity after opioid administration.
复制标题
SUR1 亚型 KATP 通道的丧失会改变阿片类药物给药后的镇痛和运动活性。
DOI：
10.1016/j.bbr.2021.113467
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发表时间：
2021
影响因子：
2.7
通讯作者：
Klein,AmandaH
中科院分区：
文献类型：
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作者：
Sakamaki,Gerald;Johnson,Kayla;Mensinger,Megan;Hmu,Eindray;Klein,AmandaH
阿片样物质信号可以通过几种下游介质发生，并影响镇痛以及神经系统中的奖赏机制。KATP通道是μ阿片受体的下游靶点，参与吗啡诱导的镇痛作用。本研究的目的是评估SUR 1亚型KATP通道在合成和半合成阿片类药物的抗伤害感受和过度运动中的作用。在给予丁丙诺啡、芬太尼或DAMGO后，评估成年雄性和雌性小鼠野生型（WT）和SUR 1缺陷型（KO）小鼠的机械和热抗伤害感受。在WT和KO小鼠的背根神经节和浅表背角细胞中评估钾通量。在丁丙诺啡、芬太尼或DAMGO给药后，还评估了WT和KO动物的过度运动。全身给予丁丙诺啡、芬太尼和DAMGO后，SUR 1 KO小鼠的机械性抗伤害感受减弱。急性给予丁丙诺啡和芬太尼后，背根神经节和脊髓背角细胞的钾通量也减弱。在SUR 1 KO小鼠中，给予吗啡和丁丙诺啡后的过度运动增强，但给予芬太尼或DAMGO后未观察到。这些结果表明，SUR 1亚型KATP通道介导了几类阿片类药物（生物碱和合成/半合成）的抗伤害性反应，但可能并不有助于所有类别的阿片类药物的“药物寻求”行为。
Opioid signaling can occur through several downstream mediators and influence analgesia as well as reward mechanisms in the nervous system. KATPchannels are downstream targets of the μ opioid receptor and contribute to morphine-induced antinociception. The aim of the present work was to assess the role of SUR1-subtype KATPchannels in antinociception and hyperlocomotion of synthetic and semi-synthetic opioids. Adult male and female mice wild-type (WT) and SUR1 deficient (KO) mice were assessed for mechanical and thermal antinociception after administration of either buprenorphine, fentanyl, or DAMGO. Potassium flux was assessed in the dorsal root ganglia and superficial dorsal horn cells in WT and KO mice. Hyperlocomotion was also assessed in WT and KO animals after buprenorphine, fentanyl, or DAMGO administration. SUR1 KO mice had attenuated mechanical antinociception after systemic administration of buprenorphine, fentanyl, and DAMGO. Potassium flux was also attenuated in the dorsal root ganglia and spinal cord dorsal horn cells after acute administration of buprenorphine and fentanyl. Hyperlocomotion after administration of morphine and buprenorphine was potentiated in SUR1 KO mice, but was not seen after administration of fentanyl or DAMGO. These results suggest SUR1-subtype KATPchannels mediate the antinociceptive response of several classes of opioids (alkaloid and synthetic/semi-synthetic), but may not contribute to the “drug-seeking” behaviors of all classes of opioids.