Treatment Responses of Procaterol and CD38 Inhibitors in an Ozone-Induced Airway Hyperresponsiveness Mice Model

Zheng Deng; Zhan-Cheng Gao; Hui-Qi Ge; Liang-Ren Zhang; Jun-Jun Zhou; Zhi-Peng Zhu; Dong-Ying Wu; Shuang-Yong Sun; Lin Chen; Xiao-Ping Pu

doi:10.1248/bpb.b13-00290

Regular Articles

Treatment Responses of Procaterol and CD38 Inhibitors in an Ozone-Induced Airway Hyperresponsiveness Mice Model

Zheng Deng, Zhan-Cheng Gao, Hui-Qi Ge, Liang-Ren Zhang, Jun-Jun Zhou, Zhi-Peng Zhu, Dong-Ying Wu, Shuang-Yong Sun, Lin Chen, Xiao-Ping Pu

Author information

Zheng Deng
State Key Laboratory of Natural and Biomimetic Drugs, Peking University
Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University
Zhan-Cheng Gao
Department of Respiratory & Critical Care Medicine, Peking University People’s Hospital
Hui-Qi Ge
State Key Laboratory of Natural and Biomimetic Drugs, Peking University
Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University
Liang-Ren Zhang
State Key Laboratory of Natural and Biomimetic Drugs, Peking University
Jun-Jun Zhou
State Key Laboratory of Natural and Biomimetic Drugs, Peking University
Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University
Zhi-Peng Zhu
State Key Laboratory of Natural and Biomimetic Drugs, Peking University
Dong-Ying Wu
State Key Laboratory of Natural and Biomimetic Drugs, Peking University
Shuang-Yong Sun
State Key Laboratory of Natural and Biomimetic Drugs, Peking University
Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University
Lin Chen
Department of Respiratory & Critical Care Medicine, Peking University People’s Hospital
Xiao-Ping Pu Corresponding author
State Key Laboratory of Natural and Biomimetic Drugs, Peking University
Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University

Keywords: airway hyperresponsiveness, CD38 inhibitor, procaterol, ozone exposure, inflammation, nuclear factor-kappaB

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Supplementary material

2013 Volume 36 Issue 8 Pages 1348-1355

DOI https://doi.org/10.1248/bpb.b13-00290

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Abstract

Airway hyperresponsiveness (AHR) and airway inflammation are key pathophysiological features of many respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). To evaluate the treatment responses of procaterol and CD38 inhibitors in an ozone-induced AHR mice model, we hypothesized that procaterol and two synthetic CD38 inhibitors (Compounds T and H) might have therapeutic effects on the ozone-induced AHR mice model, and the nuclear factor-kappaB (NF-κB) pathway and the CD38 enzymatic activity might be involved in the mechanisms. With the exception of the Control group, ozone exposure was used to establish an AHR model. Male Kunming mice in the Procaterol and CD38 inhibitors groups were treated with an emulsifier of procaterol hydrochloride, Compound T or H. Results indicated that (1) no drug showed severe toxicity in this study; (2) ozone exposure induced airway inflammation and AHR; (3) intragastric treatment with procaterol and Compound T achieved potent therapeutic effects, but Compound H did not show any therapeutic effect; (4) the NF-κB pathway was involved in both the pathogenic mechanisms of ozone and therapeutic mechanisms of procaterol and Compound T; (5) however, the in vivo effect of Compound T was not caused by its inhibitory activity on CD38. Taken together, procaterol and Compound T are potentially good drugs to treat asthma and COPD complicated with ozone exposure.

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