Rapid inhibitory effect of glucocorticoids on airway smooth muscle contractions in guinea pigs.
The common disease asthma is characterized by the obstruction, inflammation and increased sensitivity of the airways. Glucocorticoids (GCs) are one of the most potent anti-inflammatory agents available for treating allergic disease. In this study, we report that the GC budesonide (BUD) can rapidly inhibit the histamine-induced contractions of airway smooth muscle in a process mediated by non-genomic mechanisms. The tracheas of albino Hartley guinea pigs were used. We measured the effects of BUD on the increased isometric tension of trachea segment rings and the shrinking of single airway smooth muscle cells (ASMCs) induced by histamine. With the application of each reagent, the changes in the isometric tension of the segment rings upon maximum contraction and at four time points were recorded. We found that BUD significantly suppressed the increase in isometric tension induced by histamine in guinea pigs within 15 min. We also observed that BUD can reduce the histamine-induced shrinking of single ASMCs in an even shorter time. Mifepristone (RU486) and actidione did not depress the inhibitory effect of BUD. The results preclude action via genomic-mediated responses that usually take several hours to occur. We conclude therefore that GCs have a rapid non-genomic inhibitory effect on guinea pig airway smooth muscle contractions, and provide a new way to investigate this non-genomic mechanism. Further study can provide theoretical evidence for the clinical application of GCs in asthma and other allergic diseases.
Sun
Hai-Wen
HW
Laboratory of Stress Medicine, Department of Nautical Medicine, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, PR China.
Miao
Chao-Yu
CY
Liu
Lei
L
Zhou
Jian
J
Su
Ding-Fen
DF
Wang
Yun-Xia
YX
Jiang
Chun-Lei
CL
D000818:Animals; D019819:Budesonide / Q000494:pharmacology*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005938:Glucocorticoids / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000737:chemistry; D007537:Isometric Contraction / Q000187:drug effects; D015735:Mifepristone / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009924:Organ Culture Techniques; D014132:Trachea / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D005938:Glucocorticoids; D015735:Mifepristone; D019819:Budesonide; D006632:Histamine; D003513:Cycloheximide