Dynorphin A is an endogenous opioid peptide that activates orphan receptor XOR1-K+ channel, with an EC50 value of 45nM [1]. Dynorphin A can bind to and activate all members of the opioid receptor family, regulating the membrane conductance of neurons[2]. Dynorphin A has been widely used in studies related to drug dependence and addiction, as well as in the regulation of neural functions[3].
In vitro, Dynorphin A treatment at 10μM for 4 hours significantly induced caspase-3 activation in the mouse striatal neuronal cells, and increased the level of cytochrome c released from mitochondria[4]. Treatment with Dynorphin A (10μM) for 16 hours can induce a strong migration response activity in HEK293 cells that express Mac-1[5]. Treatment with 100μM Dynorphin A for 96 hours significantly induced the death of mouse spinal cord neurons [6]. Treatment with 10μM Dynorphin A for 48 hours significantly reduced the viability of U2OS cells, causing mitochondrial dysfunction and down-regulating key mitochondrial regulatory factors, including PGC-1α, Nrf1 and TFAM[7]. Treatment with 1μM Dynorphin A for 1 hour significantly inhibited the nuclear translocation of NF-κB/p65 in THP-1 cells stimulated by lipopolysaccharide (LPS) [8].
References:
[1] Zhang S, Yu L. Identification of dynorphins as endogenous ligands for an opioid receptor-like orphan receptor[J]. Journal of Biological Chemistry, 1995, 270(39): 22772-22776.
[2] Zhang S, Tong Y, Tian M, et al. Dynorphin A as a potential endogenous ligand for four members of the opioid receptor gene family[J]. The Journal of pharmacology and experimental therapeutics, 1998, 286(1): 136-141.
[3] Shippenberg T S, Zapata A, Chefer V I. Dynorphin and the pathophysiology of drug addiction[J]. Pharmacology & therapeutics, 2007, 116(2): 306-321.
[4] Singh I N, Goody R J, Goebel S M, et al. Dynorphin A (1–17) induces apoptosis in striatal neurons in vitro through AMPA/kainate receptor-mediated cytochrome c release and caspase-3 activation[J]. Neuroscience, 2003, 122(4): 1013.
[5] Podolnikova N P, Brothwell J A, Ugarova T P. The opioid peptide dynorphin A induces leukocyte responses via integrin Mac-1 (αMβ2, CD11b/CD18)[J]. Molecular pain, 2015, 11: s12990-015-0027-0.
[6] Hauser K F, Knapp P E, Turbek C S. Structure–activity analysis of dynorphin A toxicity in spinal cord neurons: intrinsic neurotoxicity of dynorphin A and its carboxyl-terminal, nonopioid metabolites[J]. Experimental neurology, 2001, 168(1): 78-87.
[7] Dai Y, Zhang J, Peng Y, et al. Dynorphin A Impairs Mitochondrial Biogenesis in Osteosarcoma Cells by Increasing SP‐1[J]. Journal of Biochemical and Molecular Toxicology, 2025, 39(9): e70451.
[8] Fazalul Rahiman S S, Morgan M, Gray P, et al. Dynorphin 1-17 and its N-terminal biotransformation fragments modulate lipopolysaccharide-stimulated nuclear factor-kappa B nuclear translocation, interleukin-1beta and tumor necrosis factor-alpha in differentiated THP-1 cells[J]. PLoS One, 2016, 11(4): e0153005.
Dynorphin A是一种内源性阿片肽，可激活孤儿受体XOR1-K+通道，EC50值为45nM[1]。Dynorphin A能结合并激活所有阿片受体家族成员，调节神经元膜电导[2]。Dynorphin A已广泛应用于药物依赖与成瘾相关研究及神经功能调控领域[3]。
在体外，使用10μM的Dynorphin A处理小鼠纹状体神经元细胞4小时，可显著诱导caspase-3活化并增加线粒体细胞色素c的释放[4]。用10μM的Dynorphin A处理表达Mac-1的HEK293细胞16小时，能诱导强烈的细胞迁移反应[5]。以100μM的Dynorphin A处理小鼠脊髓神经元96小时，可显著诱导神经元死亡[6]。用10μM的Dynorphin A处理U2OS细胞48小时，能显著降低细胞活力，引起线粒体功能障碍并下调PGC-1α、Nrf1和TFAM关键线粒体调控因子[7]。以1μM的Dynorphin A处理THP-1细胞1小时，可显著抑制脂多糖(LPS)刺激诱导的NF-κB/p65核转位[8]。