Prostaglandin D2 Induces Ca2+ Sensitization of Contraction without Affecting Cytosolic Ca2+ Level in Bronchial Smooth Muscle

被引:4
作者
Suto, Wataru [1 ]
Ando, Yusuke [2 ]
Hirabayashi, Takahiro [3 ]
Takenoya, Fumiko [1 ]
Shioda, Seiji [3 ]
Kamei, Junzo [2 ,4 ]
Sakai, Hiroyasu
Chiba, Yoshihiko [1 ]
机构
[1] Hoshi Univ, Sch Pharm, Dept Physiol & Mol Sci, Shinagawa Ku, 2-4-41 Ebara, Tokyo 1428501, Japan
[2] Hoshi Univ, Sch Pharm, Global Res Ctr Innovat Life Sci, Shinagawa Ku, 2-4-41 Ebara, Tokyo 1428501, Japan
[3] Hoshi Univ, Sch Pharm, Peptide Drug Innovat Global Res Ctr Innovat Life, Shinagawa Ku, 2-4-41 Ebara, Tokyo 1428501, Japan
[4] Hoshi Univ, Sch Pharm, Dept Biomol Pharmacol, Shinagawa Ku, 2-4-41 Ebara, Tokyo 1428501, Japan
基金
日本学术振兴会;
关键词
bronchial smooth muscle hyperresponsiveness; prostaglandin D-2 (PGD(2)); DP1; receptor; Ca2+ sensitization; RhoA; ALLERGEN-STIMULATED RELEASE; AIRWAY HYPERRESPONSIVE RATS; ASTHMA; RELAXATION; INVOLVEMENT; ANTAGONIST; RESPONSES; DISEASE; PROTEIN; CELLS;
D O I
10.3390/ijms19103036
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Prostaglandin D-2 (PGD(2)) is one of the key lipid mediators of allergic airway inflammation, including bronchial asthma. However, the role of PGD(2) in the pathogenesis of asthma is not fully understood. In the present study, the effect of PGD(2) on smooth muscle contractility of the airways was determined to elucidate its role in the development of airway hyperresponsiveness (AHR). In isolated bronchial smooth muscles (BSMs) of naive mice, application of PGD(2) (10(-9)-10(-5) M) had no effect on the baseline tension. However, when the tissues were precontracted partially with 30 mM K+ (in the presence of 10(-6) M atropine), PGD(2) markedly augmented the contraction induced by the high K+ depolarization. The PGD(2)-induced augmentation of contraction was significantly inhibited both by 10(-6) M laropiprant (a selective DP1 antagonist) and 10(-7) M Y-27632 (a Rho-kinase inhibitor), indicating that a DP1 receptor-mediated activation of Rho-kinase is involved in the PGD(2)-induced BSM hyperresponsiveness. Indeed, the GTP-RhoA pull-down assay revealed an increase in active form of RhoA in the PGD(2)-treated mouse BSMs. On the other hand, in the high K+-depolarized cultured human BSM cells, PGD(2) caused no further increase in cytosolic Ca2+ concentration. These findings suggest that PGD(2) causes RhoA/Rho-kinase-mediated Ca2+ sensitization of BSM contraction to augment its contractility. Increased PGD(2) level in the airways might be a cause of the AHR in asthma.
引用
收藏
页数:11
相关论文
共 28 条
[1]  
BJORCK T, 1992, AM REV RESPIR DIS, V145, P1087
[2]   Influenza A infection attenuates relaxation responses of mouse tracheal smooth muscle evoked by acrolein [J].
Cheah, Esther Y. ;
Mann, Tracy S. ;
Burcham, Philip C. ;
Henry, Peter J. .
BIOCHEMICAL PHARMACOLOGY, 2015, 93 (04) :519-526
[3]  
Chiba Y, 1999, RES COMMUN MOL PATH, V106, P77
[4]   Augmented acetylcholine-induced, Rho-mediated Ca2+ sensitization of bronchial smooth muscle contraction in antigen-induced airway hyperresponsive rats [J].
Chiba, Y ;
Takada, Y ;
Miyamoto, S ;
Mitsui-Saito, M ;
Karaki, H ;
Misawa, M .
BRITISH JOURNAL OF PHARMACOLOGY, 1999, 127 (03) :597-600
[5]   Involvement of RhoA-mediated Ca2+ sensitization in antigen-induced bronchial smooth muscle hyperresponsiveness in mice -: art. no. 4 [J].
Chiba, Y ;
Ueno, A ;
Shinozaki, K ;
Takeyama, H ;
Nakazawa, S ;
Sakai, H ;
Misawa, M .
RESPIRATORY RESEARCH, 2005, 6 (3-5)
[6]   Intranasal administration of recombinant progranulin inhibits bronchial smooth muscle hyperresponsiveness in mouse allergic asthma [J].
Chiba, Yoshihiko ;
Danno, Shunta ;
Suto, Rena ;
Suto, Wataru ;
Yamane, Yamato ;
Hanazaki, Motohiko ;
Katayama, Hiroshi ;
Sakai, Hiroyasu .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2018, 314 (01) :L215-L223
[7]   Antigen-induced generation of lyso-phospholipids in human airways [J].
Chilton, FH ;
Averill, FJ ;
Hubbard, WC ;
Fonteh, AN ;
Triggiani, M ;
Liu, MC .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (05) :2235-2245
[8]   The Extracellular Signal-regulated Kinase Mitogen-activated Protein Kinase/Ribosomal S6 Protein Kinase 1 Cascade Phosphorylates cAMP Response Element-binding Protein to Induce MUC5B Gene Expression via D-Prostanoid Receptor Signaling [J].
Choi, Yeon Ho ;
Lee, Sang-Nam ;
Aoyagi, Hiroki ;
Yamasaki, Yasundo ;
Yoo, Jung-Yoon ;
Park, Boryung ;
Shin, Dong Min ;
Yoon, Ho-Geun ;
Yoon, Joo-Heon .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (39) :34199-34214
[9]   PROSTANOID-INDUCED CONTRACTION OF HUMAN BRONCHIAL SMOOTH-MUSCLE IS MEDIATED BY TP-RECEPTORS [J].
COLEMAN, RA ;
SHELDRICK, RLG .
BRITISH JOURNAL OF PHARMACOLOGY, 1989, 96 (03) :688-692
[10]   Rosiglitazone elicits in vitro relaxation in airways and precision cut lung slices from a mouse model of chronic allergic airways disease [J].
Donovan, Chantal ;
Bailey, Simon R. ;
Tran, Jenny ;
Haitsma, Gertruud ;
Ibrahim, Zaridatul A. ;
Foster, Simon R. ;
Tang, Mimi L. K. ;
Royce, Simon G. ;
Bourke, Jane E. .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2015, 309 (10) :L1219-L1228