Mast cells in citric acid-induced cough of guinea pigs.
It was demonstrated previously that mast cells play an important role in citric acid (CA)-induced airway constriction. To investigate the role of mast cells in CA-induced cough, three experiments were carried out in this study. In the first experiment, 59 guinea pigs were employed and we used compound 48/80 to deplete mast cells, cromolyn sodium to stabilize mast cells, MK-886 to inhibit leukotriene synthesis, pyrilamine to antagonize histamine H(1) receptor, methysergide to antagonize serotonin receptor, and indomethacin to inhibit cyclooxygenase. In the second experiment, 56 compound 48/80-pretreated animals were divided into two parts; the first one was used to test the role of exogenous leukotriene (LT) C(4), while the second one to test the role of exogenous histamine in CA-induced cough. Each animal with one of the above pretreatments was exposed sequentially to saline (baseline) and CA (0.6 M) aerosol, each for 3 min. Then, cough was recorded for 12 min using a barometric body plethysmograph. In the third experiment, the activation of mast cells upon CA inhalation was investigated by determining arterial plasma histamine concentration in 17 animals. Exposure to CA induced a marked increase in cough number. Compound 48/80, cromolyn sodium, MK-886 and pyrilamine, but not indomethacin or methysergide, significantly attenuated CA-induced cough. Injection of LTC(4) or histamine caused a significant increase in CA-induced cough in compound 48/80-pretreated animals. In addition, CA inhalation caused significant increase in plasma histamine concentration, which was blocked by compound 48/80 pretreatment. These results suggest that mast cells play an important role in CA aerosol inhalation-induced cough via perhaps mediators LTs and histamine.
Lai
Yih-Loong
YL
Department of Physiology, National Taiwan University College of Medicine, Taipei 100, Taiwan. tiger@ha.mc.ntu.edu.tw
Lin
Tai-Yin
TY
D000336:Aerosols; D000818:Animals; D019343:Citric Acid / Q000008:administration & dosage / Q000494:pharmacology*; D003371:Cough / Q000139:chemically induced*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D017997:Leukotriene C4 / Q000494:pharmacology; D008407:Mast Cells / Q000502:physiology*
D000336:Aerosols; D019343:Citric Acid; D017997:Leukotriene C4; D006632:Histamine