Discipline of Pharmacology, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Camperdown, New South Wales 2006, Australia.
Basic and Clinical Sciences and Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Albany, New York 12208, United States.
ACS Chem Neurosci. 2020 May 6;11(9):1250-1258. doi: 10.1021/acschemneuro.9b00655. Epub 2020 Apr 9.
Glycine neurotransmission in the dorsal horn of the spinal cord plays a key role in regulating nociceptive signaling, but in chronic pain states reduced glycine neurotransmission is associated with the development of allodynia and hypersensitivity to painful stimuli. This suggests that restoration of glycine neurotransmission may be therapeutic for the treatment of chronic pain. Glycine transporter 2 inhibitors have been demonstrated to enhance glycine neurotransmission and provide relief from allodynia in rodent models of chronic pain. In recent years, photoswitchable compounds have been developed to provide the possibility of controlling the activity of target proteins using light. In this study we have developed a photoswitchable noncompetitive inhibitor of glycine transporter 2 that has different affinities for the transporter at 365 nm compared to 470 nm light.
脊髓背角中的甘氨酸神经传递在调节伤害性信号中起着关键作用，但在慢性疼痛状态下，甘氨酸神经传递减少与痛觉过敏和对疼痛刺激的敏感性增加有关。这表明恢复甘氨酸神经传递可能是治疗慢性疼痛的一种方法。甘氨酸转运体 2 抑制剂已被证明可以增强甘氨酸神经传递，并在慢性疼痛的啮齿动物模型中缓解痛觉过敏。近年来，已经开发出光致变色化合物，为使用光来控制靶蛋白的活性提供了可能性。在这项研究中，我们开发了一种光致变色的甘氨酸转运体 2 非竞争性抑制剂，与 470nm 光相比，该抑制剂在 365nm 光下对转运体具有不同的亲和力。
