Departments of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, United States.
Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, United States.
Curr Opin Pharmacol. 2020 Apr;51:29-33. doi: 10.1016/j.coph.2020.04.007. Epub 2020 May 29.
The worldwide socioeconomical burden associated with chronic respiratory diseases is substantial. Enzymes involved in the metabolism of nicotinamide adenine dinucleotide (NAD) are increasingly being implicated in chronic airway diseases. One such enzyme, CD38, utilizes NAD to produce several metabolites, including cyclic ADP ribose (cADPR), which is involved in calcium signaling in airway smooth muscle (ASM). Upregulation of CD38 in ASM caused by exposure to cytokines or allergens leads to enhanced calcium mobilization by agonists and the development of airway hyperresponsiveness (AHR) to contractile agonists. Glucocorticoids and microRNAs can suppress CD38 expression in ASM, whereas cADPR antagonists such as 8Br-cADPR can directly antagonize intracellular calcium mobilization. Bronchodilators act via CD38-independent mechanisms. CD38-dependent mechanisms could be developed for chronic airway diseases therapy.
与慢性呼吸道疾病相关的全球社会经济负担是巨大的。参与烟酰胺腺嘌呤二核苷酸（NAD）代谢的酶越来越多地与慢性气道疾病有关。其中一种酶，CD38，利用 NAD 产生几种代谢物，包括环 ADP 核糖（cADPR），它参与气道平滑肌（ASM）中的钙信号转导。暴露于细胞因子或过敏原引起的 ASM 中 CD38 的上调导致激动剂增强钙动员和对收缩性激动剂的气道高反应性（AHR）的发展。糖皮质激素和 microRNAs 可以抑制 ASM 中的 CD38 表达，而 cADPR 拮抗剂，如 8Br-cADPR，可以直接拮抗细胞内钙动员。支气管扩张剂通过 CD38 独立机制起作用。可以为慢性气道疾病治疗开发 CD38 依赖性机制。
