PMID- 28448991 OWN - NLM STAT- MEDLINE DCOM- 20170711 LR - 20190212 IS - 1421-9778 (Electronic) IS - 1015-8987 (Linking) VI - 41 IP - 6 DP - 2017 TI - Participation of Antidiuretic Hormone (ADH) in Asthma Exacerbations Induced by Psychological Stress via PKA/PKC Signal Pathway in Airway-Related Vagal Preganglionic Neurons (AVPNs). PG - 2230-2241 LID - 10.1159/000475638 [doi] AB - AIMS: Present study was performed to examine whether ADH was implicated in psychological stress asthma and to explore the underlying molecular mechanism. METHODS: We not only examined ADH levels in the cerebrospinal fluid (CSF) via radioimmunoassay, but also measured ADH receptor (ADHR) expression in airway-related vagal preganglionic neurons (AVPNs) through real-time PCR in all experimental mice. Western blotting was performed to evaluate the relationship between ADH and PKA/PKC in psychological stress asthma. Finally, the role of PKA/PKC in psychological stress asthma was analyzed. RESULTS: Marked asthma exacerbations were noted owing to significantly elevated levels of ADH and ADHR after psychological stress induction as compared to OVA alone (asthma group). ADHR antagonists (SR-49095 or SR-121463A) dramatically lowered higher protein levels of PKAalpha and PKCalpha induced by psychological stress as compared to OVA alone, suggesting the correlation between ADH and PKA/PKC in psychological stress asthma. KT-5720 (PKA inhibitor) and Go-7874 (PKC inhibitor) further directly revealed the involvement of PKA/PKC in psychological stress asthma. Some notable changes were also noted after employing PKA and PKC inhibitors in psychological stress asthma, including reduced asthmatic inflammation (lower eosinophil peroxidase (EPO) activity, myeloperoxidase (MPO) activity, immunoglobulin E (IgE) level, and histamine release), substantial decrements in inflammatory cell counts (eosinophils and lymphocytes), and decreased cytokine secretion (IL-6, IL-10, and IFN-gamma), indicating the involvement of PKA/PKC in asthma exacerbations induced by psychological stress. CONCLUSION: Our results strongly suggested that ADH participated in psychological stress-induced asthma exacerbations via PKA/PKC signal pathway in AVPNs. CI - (c) 2017 The Author(s)Published by S. Karger AG, Basel. FAU - Hou, Lili AU - Hou L AD - Department of Respiratory Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China. FAU - Zhu, Lei AU - Zhu L AD - Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Zhang, Min AU - Zhang M AD - Department of Respiratory Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China. FAU - Zhang, Xingyi AU - Zhang X AD - Department of Respiratory Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China. FAU - Zhang, Guoqing AU - Zhang G AD - Department of Respiratory Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China. FAU - Liu, Zhenwei AU - Liu Z AD - Department of Respiratory Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China. FAU - Li, Qiang AU - Li Q AD - Department of Respiratory Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China. FAU - Zhou, Xin AU - Zhou X AD - Department of Respiratory Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China. LA - eng PT - Journal Article DEP - 20170425 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (Antidiuretic Hormone Receptor Antagonists) RN - 0 (Carbazoles) RN - 0 (Cytokines) RN - 0 (Morpholines) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Pyrroles) RN - 0 (Receptors, Vasopressin) RN - 0 (Spiro Compounds) RN - 11000-17-2 (Vasopressins) RN - 58HV29I28S (KT 5720) RN - 9006-59-1 (Ovalbumin) RN - AJS8S3P31H (satavaptan) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) RN - EC 2.7.11.13 (Protein Kinase C) SB - IM MH - Animals MH - Antidiuretic Hormone Receptor Antagonists/pharmacology MH - Asthma/etiology/metabolism MH - Carbazoles/pharmacology MH - Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors/*metabolism MH - Cytokines/metabolism MH - Disease Models, Animal MH - Eosinophils/cytology/metabolism MH - Female MH - Mice MH - Mice, Inbred BALB C MH - Morpholines/pharmacology MH - Neurons/*metabolism MH - Ovalbumin/immunology MH - Protein Kinase C/antagonists & inhibitors/*metabolism MH - Protein Kinase Inhibitors/pharmacology MH - Pyrroles/pharmacology MH - Receptors, Vasopressin/chemistry/metabolism MH - Signal Transduction/drug effects MH - Spiro Compounds/pharmacology MH - *Stress, Psychological MH - Vasopressins/cerebrospinal fluid/*metabolism OTO - NOTNLM OT - Antidiuretic hormone (ADH) OT - Asthma OT - PKA/PKC OT - Psychological stress EDAT- 2017/04/28 06:00 MHDA- 2017/07/14 06:00 CRDT- 2017/04/28 06:00 PHST- 2016/07/14 00:00 [received] PHST- 2016/11/11 00:00 [accepted] PHST- 2017/04/28 06:00 [pubmed] PHST- 2017/07/14 06:00 [medline] PHST- 2017/04/28 06:00 [entrez] AID - 000475638 [pii] AID - 10.1159/000475638 [doi] PST - ppublish SO - Cell Physiol Biochem. 2017;41(6):2230-2241. doi: 10.1159/000475638. Epub 2017 Apr 25.